Search

Chimeric antigen receptor (CAR) T‐cell therapy has become a commercially available treatment option for relapsed or refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) with two or more lines of prior therapies, and recently for high‐risk r/r DLBCL with one prior line of therapy. The successful development of CAR T‐cell therapy for multiple relapsed DLBCL has led to a boom in subsequent trials that investigated its utility in patients with other r/r B‐cell lymphoma subtypes. However, CAR T‐cell therapy is a multistep process that includes leukapheresis and manipulation which take several weeks. Therefore, patients with rapidly progressing or bulky disease may not be able to complete the therapeutic regimen involving CAR T‐cell products. This raises the question of the generalizability of the results of pivotal studies to the entire population. In this review, we summarize the development of CAR‐T cell therapy for B‐cell lymphoma and discuss strategies to further improve the clinical outcomes of this treatment. [ABSTRACT FROM AUTHOR]

Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low‐tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow‐up from the first progression was 79.8 months (range, 2.1–227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4–30.2), and 76.5% (95% CI, 68.0–84.1) of the patients subsequently underwent the second‐line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6–94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4–38.8) (HR, 2.13; 95% CI, 1.48–3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first‐line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7‐NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0–25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Approximately 15% of patients with diffuse large B‐cell lymphoma (DLBCL) experience refractory or early relapsed disease after initial rituximab‐containing chemoimmunotherapy is regarded as a primary refractory disease. Although the standard treatment for relapsed DLBCL is high‐dose chemotherapy and autologous stem cell transplantation (HDC‐ASCT), the efficacy of this approach for primary refractory DLBCL is not well understood. We aimed to investigate the clinicopathological characteristics and outcomes of patients with primary refractory DLBCL. Methods: Sixty‐nine consecutive patients with primary refractory DLBCL who were treated at our institution were categorized as partial responders (partial response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone [R‐CHOP] or relapse within 6 months of R‐CHOP) (n = 41) or primary progressors (no response to R‐CHOP) (n = 28). Survival curves were constructed using the Kaplan–Meier method and compared using the log‐rank test. Results: At initial diagnosis, 70% of patients had Ann Arbor stage III/IV disease, 56% had non‐germinal center B‐cell‐like type DLBCL, and 42% had double‐expressor lymphoma (MYC and BCL2 expression). The 3‐year overall survival rate was significantly poorer in the primary progressors group than in the partial responders' group (15% vs. 48%, p < 0.001). Four of 17 patients treated with HDC‐ASCT were primary progressors; only one patient survived without relapse. Although double‐expressor lymphoma status did not significantly impact overall survival among all patients (p = 0.794), it was identified as an independent poor prognostic factor in HDC‐ASCT‐treated patients (p = 0.002). Conclusions: We identified a subgroup of patients with primary refractory DLBCL who may not benefit from current treatment strategies. Further treatment development is needed to improve the outcomes of these patients. [ABSTRACT FROM AUTHOR]

Summary: We conducted a randomised phase II study to determine the optimal dose and schedule of melphalan, prednisone, and bortezomib (MPB) (jRCTs031180097). Transplant‐ineligible untreated multiple myeloma patients were randomised to Arm A (twice weekly bortezomib in one six‐week cycle followed by eight five‐week cycles of four times once weekly bortezomib with melphalan and prednisolone on days 1–4) or Arm B (nine four‐week cycles of three times once weekly bortezomib with melphalan and prednisolone on days 1–4). The primary end‐point was complete response (CR) rate. Of 91 patients randomised to two arms, 88 were eligible. The median cumulative bortezomib doses were 45·8 and 35·1 mg/m2, CR rate was 18·6% [95% confidence interval (CI) 8·4–33·4] and 6·7% (95% CI 1·4–18·3), and the median progression‐free survival (PFS) was 2·5 and 1·4 years in Arms A and B [hazard ratio (HR) 1·93 (95% CI 1·09–3·42)], respectively. Frequent grade ≥3 haematologic toxicities in Arms A and B were neutropenia (64·4% vs. 28·3%) and thrombocytopenia (35·6% vs. 10·9%). Grade 2/3 peripheral neuropathy was observed in 24·4/2·2% in Arm A and 8·7/0% in Arm B. In conclusion, Arm A was the more promising regimen, suggesting that the twice weekly schedule of bortezomib in the first cycle and higher cumulative dose of both bortezomib and melphalan influences the efficacy of modified MPB. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the outcomes of local radiotherapy (LRT) in patients with histologic transformation (HT) following rituximab‐containing chemotherapy. Methods: We retrospectively analysed 92 patients with biopsy‐confirmed HT undergoing rituximab‐containing chemotherapy at our institution between 2003 and 2015. Results: Of the 36 patients with limited‐stage disease at diagnosis of HT, 29 (78%) received LRT. The estimated 5‐year progression‐free survival (PFS) rate was significantly better in patients who underwent LRT than in those who did not (93% and 42%, respectively; P < 0.05). Multivariate analyses employing age, sex, performance status, LRT and treatment response demonstrated that LRT was an independent prognostic factor for PFS (hazard ratio [HR]: 11.8; 95% confidence interval [CI]: 1.28‐108.1; P < 0.05). Of the 32 patients who underwent LRT for HT lesion treatment, 31 (97%) did not show disease progression within radiation fields; among them, 27 patients (84%) survived without disease progression during the follow‐up period. One patient developed hypothyroidism due to LRT; the others had no acute or late‐onset complications of LRT. Conclusions: Our data support the recommendation of LRT for HT lesion treatment following rituximab‐containing chemotherapy in select patients with localised HT, as a rational treatment approach with potentially limited toxicity. [ABSTRACT FROM AUTHOR]

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy‐proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2‐4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy. [ABSTRACT FROM AUTHOR]

Aims: The Lugano classification is a novel staging system for lymphomas established in 2014. In this staging system, 18F‐fluorodeoxyglucose‐positron emission tomography/computed tomography (FDG‐PET/CT) was formally incorporated into standard staging for FDG‐avid lymphomas, including Hodgkin lymphoma (HL). We retrospectively analyzed patients with HL who were newly diagnosed and treated at our institution to evaluate the utility of the Lugano classification compared to the Ann Arbor classification in Japanese patients with this type of lymphoma. Methods: Patients newly diagnosed with HL between 2005 and 2011 were identified through our departmental database. Data from neck‐chest‐abdomen‐pelvis CT scans, BM examinations, and FDG‐PET/CT that were routinely performed for staging at our clinical practice were retrieved and analyzed. Results: Fifty‐four patients with a median age of 35.5 years (range: 15‐78 years) were investigated in this retrospective study. The Lugano stage matched the Ann Arbor stage in 46 patients (85%). Six patients (11%) were upstaged while two (4%) were downstaged per the Lugano classification. Four patients (7%) were converted from early stage to advanced stage, but none was converted in the reverse. Among 11 patients (20%) with PET‐positive bone/bone marrow lesions, only one (2%) exhibited biopsy‐proven bone marrow involvement of HL cells. Conclusion: Our data revealed a high concordance rate between the Lugano and Ann Arbor staging system in Japanese patients with HL. Because of its low diagnostic value, routine bone marrow examination might be unnecessary for staging when FDG‐PET/CT is used as a substitute. [ABSTRACT FROM AUTHOR]

Classical Hodgkin lymphoma (cHL) is a B-cell-derived lymphoid malignancy with the most favorable prognosis among various adult malignancies. However, once it becomes refractory disease to chemotherapy or relapses after high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT), it is difficult to manage with conventional cytotoxic chemotherapy. The introduction of brentuximab vedotin (BV) has changed the treatment landscape of cHL in the past decade. Several studies demonstrated high efficacy of BV monotherapy in heavily treated patients with cHL relapsed or refractory after HDC/ASCT. Recent studies also reported high efficacy of concurrent or sequential combination of BV and chemotherapy in patients with transplant-eligible relapsed/refractory cHL at the second-line setting. In addition, a randomized phase III trial ECHELON-1 reported a positive result of BV in combination with AVD (doxorubicin, vinblastine, and dacarbazine) in patients with newly diagnosed advanced-stage cHL. In this review, we summarize available data of BV for cHL and discuss the current and future role of BV in the management of cHL. [ABSTRACT FROM AUTHOR]

Peripheral T cell lymphomas are an aggressive group of non-Hodgkin lymphomas with poor outcomes for most subtypes and no accepted standard of care for relapsed patients. This study evaluated the efficacy and safety of forodesine, a novel purine nucleoside phosphorylase inhibitor, in patients with relapsed peripheral T cell lymphomas. Patients with histologically confirmed disease, progression after ≥ 1 prior treatment, and an objective response to last treatment received oral forodesine 300 mg twice-daily. The primary endpoint was objective response rate (ORR). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. Forty-eight patients (median age, 69.5 years; median of 2 prior treatments) received forodesine. In phase 1 (n = 3 evaluable), no dose-limiting toxicity was observed during the first 28 days of forodesine treatment. In phase 2 (n = 41 evaluable), the ORR for the primary and final analyses was 22% (90% CI 12-35%) and 25% (90% CI 14-38%), respectively, including four complete responses (10%). Median PFS and OS were 1.9 and 15.6 months, respectively. The most common grade 3/4 adverse events were lymphopenia (96%), leukopenia (42%), and neutropenia (35%). Dose reduction and discontinuation due to adverse events were uncommon. Secondary B cell lymphoma developed in five patients, of whom four were positive for Epstein-Barr virus. In conclusion, forodesine has single-agent activity within the range of approved therapies in relapsed peripheral T cell lymphomas, with a manageable safety profile, and may represent a viable treatment option for this difficult-to-treat population. [ABSTRACT FROM AUTHOR]

Although MM remains incurable, treatment strategies have been improved by developing new agents and the overall survival of MM patients has significantly increased in the last decades [[1]]. In our patient, CLd therapy was effective for MM with I IgH-FGFR3 i rearrangement and VGPR was maintained for 2 years. [Extracted from the article]

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17 months, respectively, with a median follow-up of 62 months. In the 53 patients achieving CR, the median relapse-free survival (RFS) was 21 months, and 2-, 3-, and 5-year RFSs were 46, 45, and 36%, respectively. Although our results showed an unfavorable outcome for PTCL as a whole, those who achieved CR following CHOP/CHOP-like chemotherapy did not always have a poor outcome without the consolidation of HDC/auto-SCT; in particular, 45% of the 65 years or younger patients were alive without disease at 5 years. [ABSTRACT FROM AUTHOR]

We analyzed the effects of the initial approach to patients with follicular lymphoma (FL) on outcomes in order to investigate whether the watch and wait (WW) strategy is still an acceptable approach in the rituximab era. We retrospectively analyzed 348 patients who were initially diagnosed with FL between 2000 and 2012. We compared the clinical outcomes of the WW cohort and immediate treatment cohort. Among 348 patients (median age of 57 years, range: 19-85), 101 were initially managed with WW and 247 were immediately treated. The median follow-up duration was 75 months (range: 7-169). The estimated median time to treatment failure (TTF) in the treatment following WW cohort and immediate treatment cohort were 92 months (95 % CI, 60.1-NA) and 77 months (95 % CI, 65.1-107.6), respectively, which were not significantly different (P = 0.272) . In a multivariate analysis, clinical stage was identified as a predictive factor of TTF (HR 1.19, 95 % CI, 1.03-1.38, P < 0.05). Neither overall survival rate nor cumulative risk of transformation between the WW cohort and immediate treatment cohort was significant. The results of the present study suggested that the WW strategy is still an acceptable approach for selected FL patients in the rituximab era. [ABSTRACT FROM AUTHOR]

Most patients with IgA deficiency are asymptomatic, but duodenal nodular lymphoid hyperplasia is one symptom known to be associated with common variable immunodeficiency (CVID), including selective IgA deficiency and agammaglobulinemia. [ABSTRACT FROM AUTHOR]

Abstract: To evaluate the potential of allogeneic hematopoietic cell transplantation (HCT) with a reduced-intensity conditioning regimen (RIST) for the treatment of patients with hematologic malignancies not in remission, we retrospectively reviewed the medical records of 132 patients (89 leukemia or myelodysplastic syndrome, 40 malignant lymphoma, and 3 others) who received conventional myeloablative HCT (CST, n = 52) or RIST (n = 80). The median age of the RIST group was significantly higher than that of the CST group (53 years versus 40 years, P < .01). The RIST group also included a higher proportion of patients with an HCT-specific comorbidity index (HCT-CI) of 1 or more than the CST group (65% versus 37%, P = .03). The probabilities of achieving complete remission and the incidences of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) in the CST and RIST groups were, respectively, 77% and 64%, 50% and 50%, and 23% and 28%, with no significant differences. Similarly, there was no difference in the 2-year probabilities of nonrelapse mortality (NRM, 36% and 38%), progressive disease or relapse (PD 51% and 49%), overall survival (OS, 31% and 38%), and progression-free survival (PFS, 28% and 29%). Multivariate analyses revealed that a higher HCT-CI score and transplant from donors other than HLA-matched relatives were associated with increased risks of NRM and poor OS, and patients who received chemotherapy within 2 months before HCT were associated with increased risks of PD, poor OS, and PFS after transplantation. After adjusting for these variables, the risks of NRM, PD, OS, and PFS in the RIST group were not significantly different from those in the CST group. In conclusion, these results suggest that the antileukemia/lymphoma effect associated with RIST is comparable to that associated with CST. RIST appears to be feasible for the treatment of hematologic malignancies not in remission. [Copyright &y& Elsevier]

Background: The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. Methods: We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. Results: Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82–1.01), p = 0.08; I2 = 4%, p = 0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. Conclusions: G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended. [ABSTRACT FROM AUTHOR]

Secondary central nervous system involvement (sCNSi) in diffuse large B-cell lymphoma (DLBCL) is fatal. However, its features in patients with sCNSi who are categorized as lower risk by international prognostic index (IPI) or CNS-IPI are not yet fully understood. In the present analysis, we evaluated DLBCL patients who developed sCNSi at their first progression and who participated in JCOG0601, most of whom were lower risk by IPI. Of 409 patients, 21 (5.1%) developed sCNSi during a median follow-up of 4.9 years. Five-year cumulative incidence of sCNSi were 5.1%; and 4.0%, 5.3%, and 11.5% at low, intermediate, and high risk of CNS-IPI, respectively. The most common locations of extranodal lesions at the time of registration in patients with sCNSi were the stomach (n = 4), paranasal cavity (n = 3), and bone marrow (n = 2). In univariable analysis, paranasal cavity lesion was a high-risk factor for sCNSi (subdistribution hazard ratio, 4.34 [95% confidence interval 1.28–14.73]). Median overall survival after sCNSi was 1.3 years, with a 2-year overall survival rate of 39.3%. The incidence of sCNSi in DLBCL patients at lower risk of CNS-IPI was low, as previously reported, but paranasal cavity lesion might indicate high risk for organ involvement. Clinical trial registration: JCOG0601 was registered in the UMIN Clinical Trials Registry (UMIN000000929, date of registration; December 04, 2007) and the Japan Registry of Clinical Trials (jRCTs031180139, date of registration; February 20, 2019). [ABSTRACT FROM AUTHOR]

Background: Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question. Methods: The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case–control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain. Results: The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27–2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible. Conclusion: A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF) reportedly reduces the risk of neutropenia and subsequent infections caused by cancer chemotherapy. Although several guidelines recommend using G-CSF in primary prophylaxis according to the incidence rate of chemotherapy-induced febrile neutropenia (FN), the effectiveness of G-CSF in digestive system tumor chemotherapy remains unclear. To address these clinical questions, we conducted a systematic review as part of revising the Clinical Practice Guidelines for the Use of G-CSF 2022 published by the Japan Society of Clinical Oncology. Methods: This systematic review addressed two main clinical questions (CQ): CQ1: "Is primary prophylaxis with G-CSF effective in chemotherapy?", and CQ2: "Is increasing the intensity of chemotherapy with G-CSF effective?" We reviewed different types of digestive system tumors, including esophageal, gastric, pancreatic, biliary tract, colorectal, and neuroendocrine carcinomas. PubMed, Cochrane Library, and Ichushi-Web databases were searched for information sources. Independent systematic reviewers conducted two rounds of screening and selected relevant records for each CQ. Finally, the working group members synthesized the strength of evidence and recommendations. Results: After two rounds of screening, 5/0/3/0/2/0 records were extracted for CQ1 of esophageal/gastric/pancreatic/biliary tract/colorectal/ and neuroendocrine carcinoma, respectively. Additionally, a total of 2/6/1 records were extracted for CQ2 of esophageal/pancreatic/colorectal cancer, respectively. The strength of evidence and recommendations were evaluated for CQ1 of colorectal cancer; however, we could not synthesize recommendations for other CQs owing to the lack of records. Conclusion: The use of G-CSF for primary prophylaxis in chemotherapy for colorectal cancer is inappropriate. [ABSTRACT FROM AUTHOR]

Backgroud: Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. Methods: This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. Results: Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/μL), quality of life, and pain, were not apparent. Conclusions: A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN. [ABSTRACT FROM AUTHOR]

Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often preferred in the management of adverse events in the treatment of urothelial cancer. It is also important to maintain therapeutic intensity in order to control disease progression and thereby relieve symptoms, such as hematuria, infection, bleeding, and pain, as well as to prolong the survival. In this clinical question, we compared treatment with primary prophylactic administration of G-CSF to maintain therapeutic intensity with conventional standard therapy without G-CSF and examined the benefits and risks as major outcomes. A detailed literature search for relevant studies was performed using PubMed, Ichu-shi Web, and Cochrane Library. Data were extracted and evaluated independently by two reviewers. A qualitative analysis of the pooled data was performed, and the risk ratios with corresponding confidence intervals were calculated and summarized in a meta-analysis. Seven studies were included in the qualitative analysis, two of which were reviewed in the meta-analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, and one randomized controlled study showed a reduction in the incidence of FN. Primary prophylactic administration of G-CSF may be beneficial, as shown in a randomized controlled study of dose-dense MVAC therapy. However, there are no studies on other regimens, and we made a "weak recommendation to perform" with an annotation of the relevant regimen (dose-dense MVAC). [ABSTRACT FROM AUTHOR]

Background: Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. Methods: In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. Results: Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients' quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. Conclusion: G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a "weak recommendation to perform" with an annotation of the relevant regimen. [ABSTRACT FROM AUTHOR]

Introduction: The timing of prophylactic pegylated granulocyte colony-stimulating factor (G-CSF) administration during cancer chemotherapy varies, with Day 2 and Days 3–5 being the most common schedules. Optimal timing remains uncertain, affecting efficacy and adverse events. This systematic review sought to evaluate the available evidence on the timing of prophylactic pegylated G-CSF administration. Methods: Based on the Minds Handbook for Clinical Practice Guideline Development, we searched the PubMed, Ichushi-Web, and Cochrane Library databases for literature published from January 1990 to December 2019. The inclusion criteria included studies among the adult population using pegfilgrastim. The search strategy focused on timing-related keywords. Two reviewers independently extracted and assessed the data. Results: Among 300 initial search results, only four articles met the inclusion criteria. A meta-analysis for febrile neutropenia incidence suggested a potential higher incidence when pegylated G-CSF was administered on Days 3–5 than on Day 2 (odds ratio: 1.27, 95% CI 0.66–2.46, p = 0.47), with a moderate certainty of evidence. No significant difference in overall survival or mortality due to infections was observed. The trend of severe adverse events was lower on Days 3–5, without statistical significance (odds ratio: 0.72, 95% CI 0.14–3.67, p = 0.69) and with a moderate certainty of evidence. Data on pain were inconclusive. Conclusions: Both Day 2 and Days 3–5 were weakly recommended for pegylated G-CSF administration post-chemotherapy in patients with cancer. The limited evidence highlights the need for further research to refine recommendations. [ABSTRACT FROM AUTHOR]

Although granulocyte colony-stimulating factor (G-CSF) reduces the incidence, duration, and severity of neutropenia, its prophylactic use for acute myeloid leukemia (AML) remains controversial due to a theoretically increased risk of relapse. The present study investigated the effects of G-CSF as primary prophylaxis for AML with remission induction therapy. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis of pooled data was conducted, and the risk ratio with corresponding confidence intervals was calculated in the meta-analysis and summarized. Sixteen studies were included in the qualitative analysis, nine of which were examined in the meta-analysis. Although G-CSF significantly shortened the duration of neutropenia, primary prophylaxis with G-CSF did not correlate with infection-related mortality. Moreover, primary prophylaxis with G-CSF did not affect disease progression/recurrence, overall survival, or adverse events, such as musculoskeletal pain. However, evidence to support or discourage the use of G-CSF as primary prophylaxis for adult AML patients with induction therapy remains limited. Therefore, the use of G-CSF as primary prophylaxis can be considered for adult AML patients with remission induction therapy who are at a high risk of infectious complications. [ABSTRACT FROM AUTHOR]

The original version of this article contained a mistake in Fig. 4. The horizontal axis should be 36 instead of 60. [ABSTRACT FROM AUTHOR]

Although Hodgkin lymphoma has become one of the most curable lymphomas, 20-30% of patients still relapse after first-line treatment. In relapsed patients, high dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) is a standard treatment approach, however transplant-ineligible patients or patients who relapse after HDC/ASCT still have a rather poor prognosis. Immuno-checkpoint inhibitors are one of the most promising cancer immunotherapies in various advanced cancers including hematologic malignancies. PD-1-blocking antibodies have been used to enhance immunity in several malignancies and obtain durable responses, especially in the patients with heavily treated relapsed/refractory Hodgkin lymphoma. Nowadays, several clinical trials including single agent or combination therapies for Hodgkin lymphoma have been developed or are currently under investigation. The results of ongoing and future clinical trials may establish new treatment paradigm in Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Bone marrow involvement by monomorphic epitheliotropic intestinal T-cell lymphoma Flow cytometric analysis showed a small subset of CD3 SP + sp /CD8 SP + sp /CD4 SP - sp /CD5 SP - sp /CD56 SP + sp /TCR SP + sp cells, indicating bone marrow infiltration by lymphoma cells (Figure S1, bottom). Although multiple extranodal sites, including the bone marrow, may be involved in advanced stages of the disease, little is known of the cytological features of MEITL cells. [Extracted from the article]

Although Hodgkin lymphoma has become one of the most curable lymphomas, 20-30% of patients still relapse after first-line treatment. In relapsed patients, high dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) is a standard treatment approach, however transplant-ineligible patients or patients who relapse after HDC/ASCT still have a rather poor prognosis. Immuno-checkpoint inhibitors are one of the most promising cancer immunotherapies in various advanced cancers including hematologic malignancies. PD-1-blocking antibodies have been used to enhance immunity in several malignancies and obtain durable responses, especially in the patients with heavily treated relapsed/refractory Hodgkin lymphoma. Nowadays, several clinical trials including single agent or combination therapies for Hodgkin lymphoma have been developed or are currently under investigation. The results of ongoing and future clinical trials may establish new treatment paradigm in Hodgkin lymphoma. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer. Methods: We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain. Results: A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case–control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03–5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability. Conclusion: Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy. [ABSTRACT FROM AUTHOR]

Summary: Anti‐CD20 antibody in combination with chemotherapy extends overall survival (OS) in untreated advanced‐stage follicular lymphoma (FL), yet the optimal associated therapy is unclear. Data on the cumulative incidence of secondary malignancies postrelapse after conventional immunochemotherapy are scarce. A long‐term analysis of rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP) as first‐line treatment was conducted in a randomised clinical trial. A six‐cycle R‐CHOP regimen was administered every 2 or 3 weeks without rituximab maintenance. A prespecified evaluation was conducted 15 years after the completion of enrolment, following initial analysis results that showed no significant differences in outcomes at the 3‐year mark. In‐depth analyses were performed on the cohort of 248 patients with FL who were allocated to the two treatment arms. With a median follow‐up period of 15.9 years, the 15‐year OS was 76.2%. There were no protocol treatment‐related deaths, nor were there any fatal infections attributable to subsequent lymphoma treatment. At 15 years, the cumulative incidence of non‐haematological and haematological malignancies was 12.8% and 3.7% respectively. Histological transformation appeared after a median of 8 years. R‐CHOP maintains safety and efficacy in patients with advanced FL over extended follow‐up, making it a viable first‐line option for patients with advanced‐stage FL. [ABSTRACT FROM AUTHOR]

Patients with DLBCL achieving complete metabolic response (CMR) after initial treatment with R-CHOP generally have a favourable prognosis; however, there are no established prognostic biomarkers for relapse in these patients. Soluble interleukin-2 receptor (sIL-2R) levels at diagnosis are prognostic factors in patients with DLBCL. However, the significance of post-treatment sIL-2R levels is unclear. To determine the significance of post-treatment serum sIL-2R levels on subsequent relapse and survival, we retrospectively analysed 485 patients with newly diagnosed DLBCL who received R-CHOP treatment and achieved CMR. The cumulative incidence of relapse (CIR) was significantly higher in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (five-year CIR; 38.8% vs. 12.8%). The prognostic value remained significant in multivariable analysis (hazard ratio, 2.30; p < 0.001). Five-year progression-free survival (49.0% vs. 83.5%) and overall survival (61.7% vs. 91.6%) rates were lower in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (p < 0.001 for both). In patients with newly diagnosed DLBCL who achieved CMR after R-CHOP treatment, the post-treatment serum sIL-2R level was an independent prognostic marker of subsequent relapse and survival. [ABSTRACT FROM AUTHOR]

Patients with DLBCL achieving complete metabolic response (CMR) after initial treatment with R-CHOP generally have a favourable prognosis; however, there are no established prognostic biomarkers for relapse in these patients. Soluble interleukin-2 receptor (sIL-2R) levels at diagnosis are prognostic factors in patients with DLBCL. However, the significance of post-treatment sIL-2R levels is unclear. To determine the significance of post-treatment serum sIL-2R levels on subsequent relapse and survival, we retrospectively analysed 485 patients with newly diagnosed DLBCL who received R-CHOP treatment and achieved CMR. The cumulative incidence of relapse (CIR) was significantly higher in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (five-year CIR; 38.8% vs. 12.8%). The prognostic value remained significant in multivariable analysis (hazard ratio, 2.30; p < 0.001). Five-year progression-free survival (49.0% vs. 83.5%) and overall survival (61.7% vs. 91.6%) rates were lower in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (p < 0.001 for both). In patients with newly diagnosed DLBCL who achieved CMR after R-CHOP treatment, the post-treatment serum sIL-2R level was an independent prognostic marker of subsequent relapse and survival. [ABSTRACT FROM AUTHOR]

T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL) generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor), brentuximab vedotin (antibody-drug conjugate targeting CD30), chidamide (histone deacetylase inhibitor), and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody), have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients), which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL. However, it is necessary to appropriately manage opportunistic infections and secondary lymphomas possibly associated with long-lasting lymphocytopenia caused by forodesine. In this manuscript, we have summarized the currently available evidence for forodesine and discussed the clinical implications for PTCL treatment. [ABSTRACT FROM AUTHOR]

Background: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?”.A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain.Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval.This review indicated that G-CSF’s efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.Methods: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?”.A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain.Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval.This review indicated that G-CSF’s efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.Results: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?”.A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain.Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval.This review indicated that G-CSF’s efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.Conclusion: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?”.A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain.Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval.This review indicated that G-CSF’s efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Introduction: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy.A systematic literature review was conducted according to the “Minds Handbook for Clinical Practice Guideline Development” using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data.Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01–0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported.Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.Methods: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy.A systematic literature review was conducted according to the “Minds Handbook for Clinical Practice Guideline Development” using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data.Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01–0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported.Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.Results: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy.A systematic literature review was conducted according to the “Minds Handbook for Clinical Practice Guideline Development” using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data.Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01–0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported.Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.Conclusions: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy.A systematic literature review was conducted according to the “Minds Handbook for Clinical Practice Guideline Development” using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data.Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01–0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported.Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?” for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain.Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review.The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: “The benefit of primary G-CSF prophylaxis is not clear in NRC-STS” and “The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs.” G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven.Methods: Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?” for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain.Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review.The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: “The benefit of primary G-CSF prophylaxis is not clear in NRC-STS” and “The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs.” G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven.Results: Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?” for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain.Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review.The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: “The benefit of primary G-CSF prophylaxis is not clear in NRC-STS” and “The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs.” G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven.Conclusion: Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?” for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain.Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review.The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: “The benefit of primary G-CSF prophylaxis is not clear in NRC-STS” and “The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs.” G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven. [ABSTRACT FROM AUTHOR]

The prognosis of patients with aggressive adult T cell leukemia-lymphoma (ATLL) is dismal even with intensive chemotherapy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a promising option for patients with aggressive ATLL, but the posttransplant outcome remains unsatisfactory. Hence, to further improve clinical outcomes, novel therapeutic approaches are needed. The clinical significance of immune checkpoint protein expression has not been well-established in aggressive ATLL. This study aims to identify the association between the expression profile of immune checkpoint proteins on ATLL cells and clinical outcomes. This retrospective study cohort included 65 patients with aggressive ATLL diagnosed between 2001 and 2015 at the National Cancer Center Hospital, Tokyo, Japan. Formalin-fixed paraffin-embedded tissue was used to immunohistochemically determine the expression of immune checkpoint proteins and assess the impact of expression profile on the probability of overall survival from diagnosis or HSCT. The current analysis shows that cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) expressions were adverse prognostic factors in patients with aggressive ATLL. Experiments that assess the efficacy of immune checkpoint inhibitors are warranted to alleviate the adverse impacts associated with negative immune checkpoints. [ABSTRACT FROM AUTHOR]

Introduction: Excisional biopsy (EB) is considered the gold standard for lymphoma diagnosis. Although recent advances in interventional radiology enable sampling with core-needle biopsy (CNB), only few studies evaluated the utility of CNB compared to that of EB. Methods: We analyzed patients with lymphoma who had a diagnostic biopsy at the National Cancer Center Hospital during 2002–2017. We investigated the clinical and pathological characteristics of CNB in 2017. Results: The proportion of CNB utility in total biopsy procedures had increased from 11 to 48% during the 15 years. In 2017, CNB was opted more frequently than EB for a biopsy of superficial, abdominal, or anterior mediastinal lesions. Only one out of 72 patients who had CNB required re-biopsy with EB because of insufficiency. The incidence of complications was comparable between CNB and EB: 2 (4%) cases of minor bleeding with CNB and 1 (8%) case of minor bleeding with EB. The median time from the first visit to biopsy was significantly shorter with CNB (5.5 days) than with EB (15 days). Conclusion: There is an increasing trend in the utility of CNB. CNB is a less invasive method with shorter time to biopsy and can be considered an alternative to EB. [ABSTRACT FROM AUTHOR]

The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki‐67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B‐cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki‐67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression‐free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki‐67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes. [ABSTRACT FROM AUTHOR]

Durable response of therapy-related MDS/AML with concomitant Waldenström's macroglobulinemia treated with venetoclax and azacitidine Treatment recommendations for patients with Waldenström macroglobulinemia (WM) and related disorders: IWWM-7 consensus. We administered tirabrutinib retreatment, and fever, splenomegaly, and neurologic symptoms improved; however, anemia progressed and blast cells reappeared in PB. [Extracted from the article]

Objectives: In this study, we aimed to determine the clinicopathological factors influencing the treatment‐free period in patients with follicular lymphoma (FL) using a watch‐and‐wait (WW) strategy. Methods: We retrospectively assessed histopathological parameters of 82 patients with FL. Results: The median time from diagnosis to WW discontinuation was 62 months (range, 3‐138), and median follow‐up was 86 months (range, 3‐183). Intermediate or high‐risk Follicular Lymphoma International Prognostic Index score (P =.012), non‐duodenal‐type (P =.011), higher numbers of interfollicular CD4+ (P =.038) and intrafollicular FOXP3+ cells (P =.024) in the tumor microenvironment, and Ki‐67 index ≥10% (P =.031) were significant adverse factors for WW discontinuation in univariate analyses. Conclusion: Patients with adverse factors for WW discontinuation should be carefully observed during follow‐up. [ABSTRACT FROM AUTHOR]

Background: [18F] fluorodeoxyglucose-positron emission tomography is incorporated in response criteria currently used for lymphoma; however, the primary endpoint in earlier phase study is an overall response, which includes the partial response of 50% shrinkage in two dimensions. Therefore, the measurement of target lesions is still prerequisite to determine the destiny of new, promising agents. Since required is calculating the sum of the product of bidimensional diameters of maximal six target lesions, the International Workshop Criteria (IWC) used as response evaluation in lymphoma is more time-consuming than the Response Evaluation Criteria in Solid Tumors (RECIST). This study aimed to examine whether the RECIST could replace the IWC using data from a phase II/III study of R-CHOP-21 versus R-CHOP-14 for advanced-stage indolent B-cell lymphoma, JCOG0203. Methods: To evaluate the degree of agreement between them, the Kappa coefficient (KC) was calculated. Excluding patients without target lesions for the RECIST following central pathological review, 269 patients were evaluable. We determined which criterion was more predictive for progression-free survival. The criterion showing the lower point estimate of the hazard ratio (HR) of a complete response (CR) vs. a non-CR was defined as more useful. Results: The KC between them was 0.34 (95% confidence interval [CI] 0.26–0.42); namely, indicating poor agreement. The HR of the IWC (0.47: 95% CI 0.33–0.68, log-rank test p < 0.001) was lower than that of the RECIST (0.64: 95% CI 0.45–0.89, p = 0.0075). Conclusion: We conclude that unidimensional measurements cannot be substituted for the bidimensional ones for indolent lymphoma. [ABSTRACT FROM AUTHOR]

CD20− change after rituximab-containing therapy is considered one of the main reasons of rituximab resistance of B-cell non-Hodgkin lymphomas (B-NHLs). However, the clinicopathological characteristics of B-NHL with CD20− change are not entirely understood. In this study, 252 B-NHL patients who were CD20+ at initial diagnosis, whose diseases relapsed or were refractory after rituximab-containing therapy, and who were re-biopsied between 2000 and 2018, were included. The median number of rituximab administration was 11 (range, 1–48). Completely negative (cCD20−) and partially negative (pCD20−) change of CD20 was observed in 49 (20%) and 16 (6%) cases, respectively. Among cCD20− and pCD20− cases, 74% and 62% of the cases changed to CD20− at the second relapse or later, respectively. Overall survival was significantly shorter in cCD20− follicular lymphoma (FL) cases than in CD20+ FL cases. Seven histopathological patterns, such as CD20− change without histological change, histological transformation (HT) to CD20− diffuse large B-cell lymphoma, and proliferation of plasmablastic/plasmacytoid tumor cells, were associated with CD20− change. HT occurred more frequently in FLs with CD20− change than in FLs continuously expressing CD20 (P < 0.0001), regardless of the timing of HT. Nine out of 25 cases (36%) showed regain or heterogeneous regain of CD20 expression. In conclusion, 20% and 6% of the 252 B-NHL cases show cCD20− and pCD20− changes with 7 histological patterns after rituximab-containing therapy. Because changes in morphology and CD20 expression after rituximab-containing therapy vary, and recovery of CD20 expression is not rare, careful follow-up and re-biopsy in B-NHL patients are recommended. [ABSTRACT FROM AUTHOR]

This is the first case report of alectinib as a bridge to allo‐SCT in a patient with ALK‐positive ALCL refractory to both conventional chemotherapies and BV. This report offers a ray of hope for a condition with poor prognosis. [ABSTRACT FROM AUTHOR]

Summary: JCOG9801, a randomized phase III trial, reported that vincristine, cyclophosphamide, doxorubicin and prednisone (VCAP); doxorubicin, ranimustine and prednisone (AMP); and vindesine, etoposide, carboplatin and prednisone (VECP) (VCAP‐AMP‐VECP; mLSG15) showed superior clinical outcomes when compared to cyclophosphamide, doxorubicin, vincristine and prednisone every 2 weeks (CHOP‐14; mLSG19) in patients with untreated aggressive adult T‐cell leukaemia‐lymphoma (ATL). To identify patients who require VCAP‐AMP‐VECP, we conducted a supplementary analysis of JCOG9801. Overall, 105 patients were included and categorized into low‐ (n = 44), intermediate‐ (n = 54) and high‐risk (n = 7) groups according to the age‐adjusted ATL prognostic index (ATL‐PI). We excluded the high‐risk group due to small numbers of patients. VCAP‐AMP‐VECP did not show any superior trend for overall survival (OS) in the low‐risk group (hazard ratio: 1·04; 95% confidence interval: 0·54–2·04). Better OS was observed in the intermediate‐risk group treated with VCAP‐AMP‐VECP (hazard ratio: 0·65; 95% confidence interval: 0·36–1·19). In the intermediate‐risk group, the VCAP‐AMP‐VECP arm showed higher complete response rates than the CHOP‐14 arm (44·0% vs. 13·8%). The VCAP‐AMP‐VECP arm in both risk groups exhibited grade 4 thrombocytopenia, while grade 4 neutropenia was only observed in the intermediate‐risk group. VCAP‐AMP‐VECP remains suitable for the intermediate‐risk group, whereas its benefits appear modest in the low‐risk group. [ABSTRACT FROM AUTHOR]

Translocation (11;18)(q21;q21) is found in mucosa-associated lymphoid tissue (MALT) lymphoma, resulting in API2/MALT1 gene fusion. It is known that t(11;18)-positive MALT lymphoma shows a tendency to disseminate and be resistant to Helicobacter pylori eradication by antibiotics. However, the prognostic features including recurrence and histological transformation (HT) remain unknown. We conducted a single-institute retrospective analysis of 464 patients with newly diagnosed MALT lymphoma, evaluating the impact of t(11;18) on clinical outcomes. One hundred and six patients were screened for the translocation by fluorescence in situ hybridization and/or reverse transcriptase-polymerase chain reaction. Of these patients, 26 patients (25%) were diagnosed as MALT lymphoma with t(11;18). The patients had a significantly shortened progression-free survival (PFS at 10 years; 26% v 57%; P = 0.004) compared to those without t(11;18). However, this did not translate into overall survival or incidence of HT. We confirmed previous reports stating that t(11;18)-positive MALT lymphoma showed disseminated disease and refractoriness to H. pylori eradication therapy. Patients with t(11;18) had more frequent monoclonal gammopathy, especially of IgM subtype (31% v 8%; P = 0.008), some of which developed class switch. These findings characterize the features of t(11;18)-positive MALT lymphoma, suggesting that it comprises a distinct clinical entity of MALT lymphoma. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus (EBV) infection is associated with pathogenesis of various cancers, including extranodal natural killer/T‐cell lymphoma, nasal type (ENKL). ENKL tumor cells are positive for EBV‐encoded RNA1 (EBER1), which is the most useful marker to identify ENKL tumor cells in histopathology. Currently, EBER1 in situ hybridization (ISH) is recommended to evaluate bone marrow (BM) involvement of ENKL. However, the actual burden of EBER1‐positive cells in normal BM specimens remains unclear. In the present study, we performed EBER1 ISH on 111 BM specimens, which were obtained during an initial staging procedure in patients with EBV‐negative cancers and were also negative for BM involvement. One or more EBER1‐positive cells per whole specimen were observed in 38 specimens (34%). The number of EBER1‐positive cells was distributed as follows: single positive cell, n = 17; two positive cells, n = 13; three positive cells, n = 3; and four positive cells, n = 5. These findings suggest that four or fewer EBER1‐positive cells can be observed in BM specimens of patients with non‐EBV‐related cancers. The clinical implications of a small number of EBER1‐positive cells in BM specimens of patients with ENKL should be evaluated in further studies. [ABSTRACT FROM AUTHOR]