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Background: In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS). Therefore, we investigated the proportion of causative monogenic variants detected in patients who strictly met the diagnostic criteria of SRNS and explored their clinical characteristics. Methods: We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1–18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy. Results: The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (p < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)). Conclusions: Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes. [ABSTRACT FROM AUTHOR]

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is a rare blistering disease often considered a primary sign of a paraneoplastic syndrome. Retrospective studies have established its link with hematological malignancies, particularly lymphoproliferative disorders. Here, we present what we believe to be the inaugural case of successful simultaneous management of BP and de novo acute myeloid leukemia (AML) in a 28-year-old male patient. Given the rarity and severity of both conditions, our treatment strategy aimed to maximize efficacy by combining immunosuppressive therapy (initially plasmapheresis with high-dose corticosteroids, followed by anti-CD20 monoclonal antibody and intravenous immunoglobulins 2 g/m2) with lymphodepleting antileukemic chemotherapy utilizing Fludarabine (FLAG-IDA induction regimen). Following diagnosis, considering the patient's youth and the concurrent presence of two rare and potentially life-threatening diseases, we opted for an aggressive treatment. Upon achieving complete morphological remission of AML with measurable residual disease (MRD) negativity, despite incomplete resolution of BP, we proceeded with high-dose cytarabine consolidation followed by peripheral stem cell harvest and autologous stem cell transplantation (ASCT). Our conditioning regimen for ASCT involved Bu-Cy with the addition of anti-thymocyte globulins. At day + 100 post-ASCT, bone marrow evaluation confirmed morphological remission and MRD negativity. Meanwhile, BP had completely resolved with normalization of BP180 antibody levels. [ABSTRACT FROM AUTHOR]

The present study examined the therapeutic effects of preoperative neoadjuvant chemoradiation therapy (NACRT) and predictive factors for complete clinical remission, compared the prognosis and costs of abdominoperineal resection (APR) and the "watch and wait" method (WW), and evaluated the usefulness of WW. In our department, patients with stage II–III lower rectal cancer requiring APR receive NACRT. NACRT was performed as a preoperative treatment (52 Gy + S-1: 80–120 mg/day × 25 days). Eight weeks after the completion of NACRT, rectal examination, endoscopic, computed tomography, and magnetic resonance imaging findings were evaluated to assess its therapeutic effects. APR was indicated for patients in whom endoscopic findings suggested a residual tumor in which a deep ulcer or marginal swelling remained or lymph node metastasis. However, WW was selected for patients who refused APR after informed consent was obtained. In the APR and WW groups, 5- and 20-year treatment costs after CRT were calculated using the Medical Fee Points of Japan in 2020. No significant differences were observed in 3-year disease-free survival rates for either parameter between the two groups. Regarding expenses, treatment costs were lower in the WW group than in the APR group. Organ preservation using active surveillance with CRT for rectal cancer requiring APR is feasible with the achievement of endoluminal complete remission. [ABSTRACT FROM AUTHOR]

Background: A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT) or total neoadjuvant therapy (TNT) has been widely used in the clinic, but both treatment strategies are controversial. Objective: The aim of this study was to compare the oncologic outcomes of a watch-and-wait strategy or a surgical approach to treat rectal cancer in complete remission and to report the evidence-based clinical advantages of the two treatment strategies. Methods: Seven national and international databases were searched for clinical trials comparing the watch-and-wait strategy with surgical treatment for oncological outcomes in patients with rectal cancer in clinical complete remission. Results: In terms of oncological outcomes, there was no significant difference between the watch-and-wait strategy and surgical treatment in terms of overall survival (OS) (HR = 0.92, 95% CI (0.52, 1.64), P = 0.777), and subgroup analysis showed no significant difference in 5-year disease-free survival (5-year DFS) between WW and both local excision (LE) and radical surgery (RS) (HR = 1.76, 95% CI (0.97, 3.19), P = 0.279; HR = 1.98, 95% CI (0.95, 4.13), P = 0.164), in distant metastasis rate (RR = 1.12, 95% CI (0.73, 1.72), P = 0.593), mortality rate (RR = 1.62, 95% CI (0.93, 2.84), P = 0.09), and organ preservation rate (RR = 1.05, 95% CI (0.94, 1.17), P = 0.394) which were not statistically significant and on the outcome indicators of local recurrence rate (RR = 2.09, 95% CI (1.44, 3.03), P < 0.001) and stoma rate (RR = 0.35, 95% CI (0.20, 0.61), P < 0.001). There were significant differences between the WW group and the surgical treatment group. Conclusion: There were no differences in OS, 5-year DFS, distant metastasis, and mortality between the WW strategy group and the surgical treatment group. The WW strategy did not increase the risk of local recurrence compared with local resection but may be at greater risk of local recurrence compared with radical surgery, and the WW group was significantly better than the surgical group in terms of stoma rate; the WW strategy was evidently superior in preserving organ integrity compared to radical excision. Consequently, for patients who exhibit a profound inclination towards organ preservation and the evasion of stoma formation in the scenario of clinically complete remission of rectal cancer, the WW strategy can be contemplated as a pragmatic alternative to surgical interventions. It is, however, paramount to emphasize that the deployment of such a strategy should be meticulously undertaken within the ambit of a multidisciplinary team's management and within specialized centers dedicated to rectal cancer management. [ABSTRACT FROM AUTHOR]

The prognostic significance of WT1 expression at diagnosis in acute myeloid leukemia (AML) remains obscure, and subgroup analysis is the way for clarification. We previously reported the results in t(8;21) AML. In this study, 437 consecutive adult AML patients with non-favorable cytogenetic risk were enrolled. All patients were tested WT1 transcript levels using real-time quantitative PCR at diagnosis; AML-related common fusion genes, KMT2A-PTD, FLT3-ITD, NPM1, CEBPA and TP53 mutations were simultaneously tested. 92.4% of patients overexpressed WT1 compared to normal bone marrow. The existence of FLT3-ITD, NPM1 mutation and the absence of CEBPA biallelic mutation were significantly related to higher WT1 expression. The cutoff value for WT1 was determined by performing receiver operating characteristic curve analysis in regard to complete remission (CR) achievement and was used to categorize patients into low-expression (WT1-L) and high-expression (WT1-H) groups. In the entire cohort, WT1-H was significantly associated with a lower 1-course and 2-course CR rate (P < 0.0010 and P = 0.0060) but was not related to relapse-free survival (RFS). Multivariate analysis showed that WT1-H was an independent adverse prognostic factor for both 1-course and 2-course CR achievement. Subgroup analysis was further performed. WT1-H had a significant adverse impact on CR achievement within intermediate-cytogenetic risk, high-cytogenetic risk, ELN-defined-intermediate-risk, normal karyotype, KMT2A rearrangement, FAB-M2, FAB-M5 and NPM1 mutation (+) subgroups, whereas it had no impact within ELN-defined-low-risk, ELN-defined-high-risk, FAB-M4, FLT3-ITD mutation (+) and CEBPA biallelic mutation (+) subgroups. Moreover, WT1-H patients had a significantly lower RFS rate than WT1-L patients within both FAB-M5 and KMT2A rearrangement subgroups (P = 0.010 and 0.028), whereas WT1 had no impact on RFS within other subgroups mentioned above (all P > 0.05). Therefore, high WT1 expression at diagnosis independently predicted induction chemotherapy failure in AML patients with non-favorable cytogenetic risk, and it was related to relapse just within FAB-M5 and KMT2A rearrangement subgroups. [ABSTRACT FROM AUTHOR]

Early T-cell precursor lymphoblastic leukemia (ETP-ALL) has a unique immunophenotype with very early T-cell differentiation. The current study summarises the distinct clinicopathological aspects of ETP-ALL and compares them with non-ETP-ALL. Twenty-nine ETP-ALL and 191 non-ETP-ALL cases were retrieved between 2018 and 2021. A P value was determined for each of the patient charaterisics (Table 1) to see for any significant relationship (P < 0.05) with ETP-ALL versus non-ETP-ALL. Kaplan–Meier log rank test was applied to look for any significant differences in OS for both the ALLs. ETP-ALL had an incidence of 12.6% out of total T-Acute lymphoblastic leukemia (T-ALL/LBL) in the past 3-years. Compared to non-ETP-ALL, ETP-ALL cases were associated with lower median age and male-to-female ratio. There was no statistically significant difference in the complete remission rate between both the subtypes. ETP-ALL was seen to be associated with high induction failure and relapse rate compared to non-ETP-ALL. To summarise, since the 2-year OS was poor compared to western research (for both ALLs), an intensive chemo-regimen should be implemented in the current situation. Some unusual markers were observed on flow-cytometry (ETP-ALL), which can be useful for MRD quantification, prognosis, and further trials for newer targeted therapies. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy is not uncommon for clinical practice. Within multiple options of treatment, it is alternatively to consider less well-studied immunosuppressants such as calcineurin inhibitors (CNI). The knowledge of CNI with steroid in the treatment of IgA nephropathy can be clarified via a systematic review and meta-analysis of randomized clinical trials. Methods: We performed the systematic search and meta-analysis for the randomized clinical trials of the CNI treatment in IgA nephropathy. The comparison between CNI combined with steroid and steroid-alone treatment was performed to find if the CNI combined with steroid can achieve more complete remission for IgA nephropathy. In addition, the related treatment effects were analyzed. After restricted selection, 16 studies with a total of 998 subjects with IgA nephropathy were enrolled. The focused outcome was complete remission, proteinuria, serum creatinine, and estimated glomerular filtration rate. Results: The meta-analysis showed higher odds ratio of complete remission if the patients received CNI with steroid combined treatment. The proteinuria can be significantly reduced under the combined treatment of CNI and steroid. However, the CNI with steroid combined treatment showed a non-superior effect on the parameters of serum creatinine and estimated glomerular filtration rate. Conclusions: In current meta-analysis, the CNI combined with steroid treatment might show a trend to achieve complete remission status and reduce the proteinuria of IgA nephropathy when compared to steroid-alone treatment. However, no significant effects were observed in parameters of serum creatinine and estimated glomerular filtration rate. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between immunohistochemical characteristics and recurrence after complete remission (CR) with fertility preservation treatment in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (AH). Methods: The clinical data and immunohistochemical results of 53 patients with EC and 68 patients with AH admitted to Peking University People's Hospital from January 2010 to January 2021 were retrospectively analyzed. Patients were divided into two groups according to whether recurrence after complete remission (CR): group 1: recurrence after CR; group 2: no recurrence after CR, for statistical analysis. Results: (1) The expression rate of ER in group 1 was lower than that in group 2, (P < 0.05). The expression rate of Ki-67 in group 1 was significantly higher than that in group 2, (P < 0.01). The expression rates of PR, P16, P53, and PTEN were not significantly different between the two groups (P > 0.05); (2) combination index ER/ Ki-67 row ROC curve analysis, there was a significant difference (P < 0.01), the best cut-off value was 3.55, sensitivity 0.730, specificity 1.000, Youden index 0.730. The 3-year RFS of high rate patients was 100%, and that of low rate patients was 42.3%, P < 0.01. Conclusions: The expression rate of Ki-67 is of great significance in predicting the recurrence of EC after fertility preservation therapy. The best cut-off value of combination index ER/ Ki-67 (3.55) was better than a single immunohistochemical marker in predicting recurrence of EC after fertility preservation treatment. [ABSTRACT FROM AUTHOR]

A randomized inter-group trial comparing more intensive treatment strategies to a common standard arm 3 + 7 (CSA) was conducted in patients with non-M3 AML. Untreated patients ≥ 60 years were allocated to the CSA (n = 132) or to the study group arms (n = 1154) of the AMLCG (TAD/HAM versus HAM/HAM ± G-CSF followed by TAD and maintenance) and the OSHO (intermediate-dose ara-C/mitoxantrone followed by ara-C/mitoxantrone). Median age of the 1147 eligible patients was 69 (range 60–87) years. CR/CRi status at 90 days was not significantly different between the CSA (54% (95%CI: 45–64)) and the study group arms (53% (95%CI: 47–60) and 59% (95%CI: 58–63)). The five-year event-free survival (EFS) probability (primary endpoint) was 6.2% (95%CI: 2.7–14.0) in the CSA, 7.6% (95%CI: 4.5–12.8) in study group A and 11.1% (95%CI: 9.0–13.7) in B. The 5-year OS was 17.2% (95%CI: 11.0–26.9), 17.0% (95%CI: 2.0–23.9), and 19.5% (95%CI: 16.7–22.8) in CSA, study group A and B, respectively. Neither study group differed significantly from the CSA regarding EFS, OS, or relapse-free survival. In multivariate analyses, allocation to the treatment strategy was not significantly associated with the time-to-event endpoints. The evaluation of more intensive treatment strategies did not show clinically relevant outcome differences when compared to CSA. [ABSTRACT FROM AUTHOR]

A standard salvage regimen for patients with acute myeloid leukemia (AML) who are not in complete remission (CR) after initial induction therapy does not exist. We retrospectively investigated re-induction therapy for 151 patients with AML who did not achieve CR after the initial course between January 2014 and March 2021. The re-induction regimen did not correlate with the CR rate after the second course, whereas patients had similar 5-year overall survival (OS) and event-free survival (EFS) based on different re-induction regimens. Multivariable analysis revealed that International European Leukaemia Net (ELN) risk stratification independently predicted both OS and EFS among patients not in CR after the first course, although the re-induction regimen did not predict prognosis. Urgent salvage alloHSCT may improve the prognosis of patients with refractory AML. In summary, our study showed that the re-induction regimen did not significantly predict the prognosis of patients with AML not in CR after the first course of treatment. The development and selection of an efficient treatment algorithm for the treatment of AML remains a pressing research challenge. [ABSTRACT FROM AUTHOR]

Background: Minimal change nephrotic syndrome (MCNS) is a common type of nephrotic syndrome in adults, though evidence regarding its clinical and histopathological features related to time to complete remission (CR) is limited. Methods: This was a retrospective study of biopsy-proven, first-onset, adult MCNS patients who achieved CR after undergoing corticosteroid treatment. Body weight (BW) change rate was calculated as follows: (BW at admission − BW at discharge)/BW at discharge × 100. Histopathological examinations were performed, with particular attention given to tubulointerstitial lesions. Results: Fifty-seven patients (median 41 years old, range 22–63 years; 37 males) were diagnosed with MCNS from 2007 to 2020. Time to CR was a median 11 (8–21) days. In addition to serum creatinine and urinary protein, BW change rate also showed a positive correlation with time to CR (rs = 0.438, p < 0.001; rs = 0.280, p = 0.035; rs = 0.544, p < 0.001; respectively), while multivariate Cox proportional hazards models also revealed those factors as significant predictors for longer time to CR. In MCNS patients with a higher BW change rate (n = 28), serum creatinine, urinary protein, histopathological score, and time to CR were significantly greater as compared to those with a lower BW change rate (n =29). Also, in those patients, histopathological interstitial edema was significantly associated with longer time to CR after adjustments for serum creatinine and urinary protein. Conclusion: The present results indicate that BW change rate can predict time to CR in adult-onset MCNS patients. Histopathologically, interstitial edema is also an important factor for time to CR in MCNS patients with greater BW increase. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to compare outcomes of patients with AML treated with frontline hypomethylating agent and venetoclax (HMA + Ven) who achieved complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), or morphologic leukemia-free state (MLFS) as defined by ELN 2022. Methods: Patients with AML seen at Moffitt Cancer Center between 2018 and 2022 and treated with HMA + Ven were retrospectively evaluated. Results: About 120 patients achieved blast clearance with best response of CR in 52 (43.3%), CRh in 22 (18.3%), CRi in 31 (25.8%) and MLFS in 15 (12.5%) patients. Greater proportion of patients with MLFS had a prior myeloid malignancy (p = 0.003) and were treated with prior HMA (p < 0.001). Patients that achieved MLFS as their best response had inferior OS compared to the CR/CRh/CRi cohort (8 months vs. 27 months; p < 0.001). RFS was also worse for the MLFS cohort. Conclusion: To the best of our knowledge, this is the largest study analyzing differences in outcomes of AML patients treated with HMA + Ven based on best response. We noted that prior myeloid malignancy and use of HMA led to more MLFS as best response compared to CR/CRi. The OS and RFS were inferior for MLFS cohort. [ABSTRACT FROM AUTHOR]

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Summary: Diffuse midline gliomas (DMGs), which are malignant, fast-growing and entail a poor prognosis, are a rare subtype of glial tumor. DMGs harboring H3 K27-mutation are a novel entity with a poorer prognosis than the H3 wildtype and are categorized as a grade IV glioma. Histone-mutated DMGs characterized by a midline location occur more commonly in children and less frequently in adults. Considering the DMG treatment is limited, there is an urgent need for effective therapeutic strategies. Olaparib is a poly-adenosine diphosphate-ribose polymerase inhibitor, which has been reported to inhibit glioma in preclinical and clinical trials. Olaparib plus bevacizumab has been successfully used in ovarian cancer. However, the application of olaparib in DMGs has not been reported yet. Herein, we firstly reported that an adult DMG patient benefited from olaparib combined with bevacizumab and achieved complete remission. The duration of response and overall survival was 8 months and 16 months respectively. This report provides a promising treatment option for patients with DMG. [ABSTRACT FROM AUTHOR]

Opinion Statement: Acute lymphoblastic leukemia (ALL) in adults is associated with poor outcomes as compared to children when treated with chemotherapy, leading to a considerably inferior cure rate. Historically, consolidation with allogeneic hematopoietic cell transplant (alloHCT) was routinely recommended for eligible adults with ALL in first complete remission (CR1) if a donor was available, since randomized studies showed superiority over continuing chemotherapy. With the increasing use of pediatric-inspired frontline regimens in young adults with ALL and the availability of novel salvage agents for relapsed/refractory B-cell ALL that have high potential in inducing a second CR, the role of early alloHCT in the treatment paradigm for ALL needs to be reevaluated, and the decision should be individualized for each patient. Simultaneously, alloHCT has evolved considerably lately, and historical randomized studies that have proven the benefit of alloHCT in adults with ALL in CR1 did not included the increasing use of reduced intensity conditioning and haploidentical transplants, and therefore, data may not entirely apply. Nowadays, detectable minimal residual disease (MRD) is the most prognostic determinant of ALL outcome and should be a major consideration in the decision to perform alloHcT in CR1. Nonetheless, other biological and clinical factors remain relevant and can support the complex decision-making. Such factors include high-risk leukemia genetics, the type of administered chemotherapy regimen and the ability of the patient to tolerate all key components of the regimen, and the availability of effective salvage therapies that allow alloHCT to be performed in CR2 in case of relapse after chemotherapy. [ABSTRACT FROM AUTHOR]

There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option. [ABSTRACT FROM AUTHOR]

Transanal resection procedures are special surgical methods for the minimally invasive treatment of rectal tumors. Apart from benign tumors, this operative procedure is suitable for the excision of so-called low-risk T1 rectal carcinomas, if these can be completely removed up to healthy tissue (R0 resection) due to the size and localization. With stringent patient selection very good oncological results are achieved. Various international trials are currently evaluating whether local resection procedures are oncologically sufficient when there is complete or near complete remission after neoadjuvant radiotherapy/chemotherapy. Numerous studies have confirmed that in particular the functional results and the postoperative quality of life after local resection are excellent, especially considering the well-known functional deficits of alternative operations, such as low rectal resection or abdominoperineal extirpation. [ABSTRACT FROM AUTHOR]

A 69-year-old woman who had a history of chronic hepatitis C, autoimmune hemolytic anemia and myelodysplastic syndrome was treated with sorafenib at a daily dose of 400 mg for HCC with multiple lung metastases. Nonetheless, elevated serum tumor markers further increased (alpha fetoprotein from 121,100 to 348,660 ng/ml and protein induced by vitamin K absence/antagonist-II from 3435 to 29,357 mAU/ml), and lung metastatic lesions on chest X-ray showed no improvement after 2 months of sorafenib treatment. Sorafenib was discontinued because of adverse events with diarrhea, fatigue, and severe anemia due to bleeding from stomach telangiectasia. Hand–foot syndrome was mild. Thereafter, the tumor markers rapidly decreased to almost normal range, and the lung and liver tumors markedly shrunk and disappeared without any other cancer treatments. Her tumors remained in complete remission for 17 months until an intrahepatic recurrence occurred. This unique course of metastatic HCC indicated that antitumor mechanisms other than the direct anticancer effect of sorafenib contributed to tumor shrinkage. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the early remission rate of type 2 diabetes mellitus (T2DM) after laparoscopic sleeve gastrectomy (LSG) and establish a preliminary scoring system that predicts T2DM remission. Methods: We assessed the outcomes of 49 morbidly obese patients with T2DM who underwent LSG between 2008 and 2018. The prognostic factors for T2DM remission 1 year post-LSG were identified and an original scoring system was established. We validated our scoring system by comparing it with the individualized metabolic surgery score and the ABCD score. Results: The patients' mean body weight loss and percentage of excess weight loss were 34.4 kg and 59.4%, respectively, while the T2DM remission rate was 77.5%. The serum insulin level and the T2DM duration were independent predictive factors, the receiver-operating characteristic (ROC) curves for which revealed cutoff values of 12.7 ng/mL and 72 months, respectively. We set our system's score range at 0–2, whereby patients with higher scores have a good T2DM remission prognosis, as higher insulin levels, and/or shorter T2DM duration. Our scoring system had accuracy levels similar to those of the ABCD score with a simple stratification. Conclusion: Our preliminary scoring system attains a good level of accuracy for predicting T2DM remission. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the predictive value of the in vitro chemosensitivity using ATP-TCA method to compare the clinical efficacy of patients with AML.Methods: Bone marrow or peripheral blood samples were collected from 65 patients with AML, and the in vitro chemosensitivity of four drugs (cytarabine/idarubicin/decitabine/aclacinomycin) was measured by an ATP-tumor chemosensitivity assay.Results: Aclacinomycin and cytarabine had the highest chemosensitivity rates (66.7%, 8/12 and 58.5%, 38/65, respectively), while idarubicin and decitabine had rates of 6.5% (3/46) and 0% (0/35), respectively. Complete remission (CR) was achieved in 66.2% (43/65) of patients, and there was a statistically significant correlation between CR and in vitro chemosensitivity for cytarabine (47.7% vs 18.5%, p = 0.002), but not for the anthracyclines (p = 0.950). In addition, three other factors significantly correlated with CR: disease status (p = 0.005), FLT3-ITD/TKD mutation (p = 0.003) and chemotherapy regimens (p = 0.004). Furthermore, multiple logistic regression analysis revealed that the sensitivity of cytarabine was one of the significant risk factors for CR [hazard ratio (HR) = 5.52; 95% confidence interval (CI) = 1.47-20.70; p = 0.011].Conclusions: The in vitro chemosensitivity as tested by ATP-TCA demonstrated a significant correlation with CR for chemotherapy and can be a useful tool to optimize personalized treatments for patients with AML. [ABSTRACT FROM AUTHOR]

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The overall survival (OS) in patients with multiple myeloma (MM) has increased in the last decade due to the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies as well as an extensive combination of autologous stem cell transplantation (ASCT) for suitable patients. The objective of this study was to examine the impact of pre-transplant and post-transplant remission status of patients on survival in newly diagnosed multiple myeloma. Two hundred and four patients with newly diagnosed MM who received an ASCT in our HSC transplant center at Hacettepe University Hospital between the years of 2001 and 2018 were evaluated in a retrospective manner. The median follow-up period was 35.9 months (range 4.2–206.4) for the entire group. The 5-year OS for pre-transplant remission status CR/VGPR patients and pre-transplant remission status PR or less patients were 79% and 68%, respectively (p = 0.09). The 5-year PFS for pre-transplant remission status CR/VGPR patients and pre-transplant remission status PR or less patients were 62% and 45%, respectively (p = 0.23). The 5-year OS for post-transplant remission status CR/VGPR group was 72% and for post-transplant remission status PR or less group was 60% (p = 0.02). The 5-year PFS in post-transplant remission status CR/VGPR patients was 48% and post-transplant remission status PR or less patients was 36% (p = 0.03). This study focuses on determination of survival outcome based on the best response obtained before and after ASCT and particularly highlights the significance of reaching CR and VGPR. [ABSTRACT FROM AUTHOR]

The objective is to assess quality-of-life (QoL) parameters among Indian female systemic lupus erythematosus (SLE) patients with durable remission. Indian female SLE patients in remission determined by the European consensus criteria and age-matched female control participants were included in the study. All included participants underwent measurements of QoL [Medical Outcomes Study Short-Form-12 (SF12)], Fatigue Severity Scale, and structured interview with a clinical psychologist. The population comprised of 126 female SLE patients [median age: 27.5 years [interquartile range (IQR): 11]; median disease duration: 36 months (IQR 26)] and 110 female controls [median age 30 years (IQR 9)]. Clinical remission was seen in 65.9% (83/126) and complete remission in 34.1% (43/126). Significant fatigue was present in 18.3% (23/126). Both SF-12 physical component summary (PCS) and mental component summary (MCS) were similar between SLE patients and controls [median PCS: 50.3 (IQR: 16.2) vs. 48.6 (IQR: 11.6); median MCS: 57.2 (IQR: 4.8) vs. 57.9 (IQR: 7.6)]. In generalised linear modelling, PCS was associated with fatigue [odd's ratio (OR) 0.012, 95% confidence interval (CI) 0.006–0.025, p < 0.001], disease duration ≥ 5 years (OR 23.16, 95% CI 1.548–346.58, p = 0.023), and complete remission (OR 33.16, 95% CI 4.43–248.15, p = 0.001); MCS with fatigue (OR 0.53, 95% CI 0.34–0.84, p = 0.007) and absence of depression (OR 3.65, 95% CI 1.07–12.44, p = 0.038). Patients with SLE in remission report significant fatigue in 18.3% of subjects. Both PCS and MCS scores are similar to healthy controls. Better PCS was associated with less fatigue, longer disease duration, and complete remission. Better MCS was associated with less fatigue and absence of depression. [ABSTRACT FROM AUTHOR]

Background: Wilms tumor 1 (WT1) gene is overexpressed in numerous cancers, including acute myeloid leukemia (AML). The alternative WT1 gene (AWT1) is generated from alternative transcription start site in the WT1 first intron and encodes an N-terminal-truncated protein lacking the repressor domain. Although WT1 overexpression is a common feature in AML, the expression levels of the AWT1 and its underlying epigenetic alterations, as well as their clinical relevance in AML remain unknown. Methods: Quantitative assessment of AWT1 gene transcripts was performed using real-time polymerase chain reaction (PCR). Bisulfite PCR followed by pyrosequencing was done to determine the methylation status of the AWT1 promoter. The bone marrow samples were collected at diagnosis and after completion of induction chemotherapy from 80 newly diagnosed AML patients. Forty non-malignant BM samples were recruited as controls. Results: The AWT1 was significantly overexpressed in AML patients. Robust hypermethylation of the AWT1 promoter was found to be a highly specific and sensitive marker for AML (p < 0.001). Significant positive correlations between the AWT1 expression and methylation levels with BM blast counts at both initial diagnosis and after induction therapy were observed (p < 0.001). AWT1 overexpression at the initial diagnosis of AML was found to be an independent negative factor for complete remission response after induction therapy (p = 0.014). Conclusion: The AWT1 gene overexpression–hypermethylation signature is a characteristic marker that positively correlates with the leukemic burden in AML. AWT1 overexpression at AML diagnosis is an independent negative predictor for CR after induction chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: In the absence of head-to-head trials, this analysis aimed to provide a fair indirect comparison of the efficacy between blinatumomab and inotuzumab ozogamicin (InO), two treatments for adult patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL) who received no more than one prior salvage therapy, by adjusting for cross-trial differences.Methods: Patient-level data from the Phase 3 blinatumomab trial TOWER and published aggregated data from the Phase 3 InO trial INO-VATE-ALL were used to conduct matching-adjusted indirect comparisons. Patients with 2+ prior salvage therapies from TOWER were excluded because such patients were not included in INO-VATE-ALL. To ensure balance in the remaining patients, baseline characteristics for the TOWER patients were weighted to match the average baseline characteristics in INO-VATE-ALL, including sex, age, race, performance status, bone marrow blast, previous salvage therapy, previous allogeneic transplantation, complete remission with complete hematologic recovery (CR) to most recent induction therapy, and duration of first remission. Overall survival (OS), including median and restricted mean survival time (RMST) at 12 and 20.7 months, and CR were estimated and compared.Results: A total of 310 patients in TOWER were included (blinatumomab, n = 203; standard of care chemotherapy, n = 107). After matching the listed baseline characteristics, the median OS was 9.3 months for blinatumomab and 7.7 months for InO (weighted log-rank test p = 0.4). The relative RMST at 12 months was 1.6 months longer for blinatumomab than for InO [95% CI (0.1, 3.2); p = 0.04]; at 20.7 months the RMST was not significantly different. The CR rates were similar [anchor-based difference = - 2.8%, 95% CI (- 17.5%, 11.9%); p = 0.71].Conclusions: After adjusting for cross-trial differences, blinatumomab demonstrated a similar CR rate and potential OS benefit versus InO among adult patients with R/R ALL who received no more than one prior salvage therapy. Further studies are suggested to confirm this finding.Funding: Amgen. [ABSTRACT FROM AUTHOR]

Objective: The relation of absolute lymphocyte count (ALC) with minimal residual disease (MRD) in T cell - acute lymphoblastic leukemia (T-ALL) is not known. The objective of the study was to correlate ALC with MRD, steroid-response and complete remission (CR). Methods: De-novo T- ALL patients (age 1–18 y) recruited prospectively; 52 enrolled, 9 excluded, and 43 analyzed. 39 achieved CR and MRD was available for 28 patients; 23 were MRD negative. Results: ALC did not correlate with steroid response and CR. Median (range) ALC at the end of induction was significantly higher in patients who were MRD negative compared to MRD positive [1.24 (0.12, 6.69) vs 0.62 (0.15, 0.87); P=0.03], respectively. Patients having ALC ≥700×109 /L were significantly more likely to be MRD negative than those with lower values (P= 0.028) Conclusion: Our study suggests that ALC is a favorable factor, and may act as surrogate marker for MRD. [ABSTRACT FROM AUTHOR]

To compare the efficiency of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) against that of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) for treating Hodgkin lymphoma (HL). An extensive English-language literature retrieval on clinical outcomes after treatment by ABVD versus BEACOPP was conducted on Medline, PubMed, and Embase through the period ending December 2015. Odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was pooled based on the heterogeneity across individual studies. In total, seven articles reporting on four trials were included in this meta-analysis. Patients assigned to BEACOPP therapy had a better complete remission (CR) rate (OR = 0.55, 95 % CI 0.35, 0.87), overall survival (OS) greater than 5 years (OR = 0.64, 95 % CI 0.51, 0.81), and progression-free survival (PFS, OR = 0.56, 95 % CI 0.38, 0.81) than patients assigned to ABVD therapy. Subgroup analysis stratified using a different strategy showed no significant difference for OS between short courses of escalated BEACOPP combined with standard BEACOPP and that for ABVD (OR = 0. 72, 95 % CI 0. 45, 1.15). Reduced progression/relapse, better CR, and similar OS were observed with BEACOPP, indicating its superior efficiency of BEACOPP in the treatment of HL. However, more analysis of treatment-related toxicity is needed. [ABSTRACT FROM AUTHOR]

The outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) has improved with the use of tyrosine kinase inhibitors, such as imatinib and dasatinib. We report a 63-year-old woman with Ph-ALL who maintained complete remission for 10 years using imatinib without high-intensity chemotherapy or allogeneic stem cell transplantation. She underwent induction therapy with imatinib plus prednisolone and achieved complete remission by day 53. Imatinib was continued until 103 months, when it was stopped in response to renal dysfunction; however, the patient continued to exhibit molecular remission at 120 months. This is the first report in the literature describing a patient with Ph-ALL who achieved remission for more than 10 years after treatment only with imatinib. [ABSTRACT FROM AUTHOR]

Background: Data on global (IV-G) and segmental (IV-S) diffuse proliferative lupus nephritis (DPLN) in children are lacking. Methods: To determine the clinicopathology and prognosis of DPLN subclasses IV-G and IV-S, we analyzed the clinical, laboratory, and demographic data of 56 children aged <18 years diagnosed with DPLN [36 (64.3 %) with IV-G; 20 (35.7 %) with IV-S] between 2004 and 2013. Clinical endpoints were: (1) complete remission (CR), (2) chronic kidney disease [CKD; defined as estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m or end-stage renal disease (ESRD)], and (3) death. Results: Proteinuria and the activity index were higher in patients with IV-G ( p < 0.05). Global endocapillary proliferation and leukocyte exudation were predominant in IV-G patients, whereas segmental endocapillary proliferation was predominant in patients with IV-S ( p < 0.005). CR rates in IV-G and IV-S patients were 50 and 60 %, respectively ( p = 0.47). Renal survival rates, defined as an eGFR of ≥60 mL/min/1.73 m, were 93, 78, and 64 % at 1, 5, and 10 years, respectively. Patient survival rates at 1, 5, and 10 years were 98, 96, and 91 %, respectively. Patient and renal survival rates were similar in both subclasses. Conclusions: Although patients with IV-G and IV-S displayed some clinical and histopathological disparities, renal outcomes were similar. The majority of children with DPLN reached adulthood but accrued significant renal damage. Treatment regimens which can slow the progression of CKD are needed. [ABSTRACT FROM AUTHOR]

B-cell lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) proteins are anti-apoptotic and pro-apoptotic determinants of mitochondrial-mediated apoptosis, and their relative expression determines the cell fate. The promoter polymorphisms in these genes were shown to alter the protein function or expression and exert an impact on apoptosis regulation. Deregulation in the expression of any of these genes leads to disruption of cellular homeostasis and malignant transformation. The present study was aimed to determine the association of BCL2-938C>A and BAX-248G>A promoter polymorphisms with origin and progression of acute myeloid leukemia (AML). We also have performed combined genotype analysis to evaluate the cumulative effect of risk genotypes in the AML development. These polymorphisms were genotyped by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) in 221 AML patients and 305 age- and sex-matched healthy controls. Our study revealed that BCL2-938CA ( p = 0.018) and BAX-248GG (0.043) genotypes were significantly associated with increased risk for AML occurrence. BAX-248A allele had shown decreased risk for AML. The combined analysis had shown that BCL2-938CA+AA-BAX-248GG group had a 1.63-fold (95 % CI: 1.08-2.45, p = 0.02) increased risk for AML. None of the clinical variables had shown any significant association with both polymorphisms. With respect to complete remission (CR) rate, BAX-248GG genotype ( p = 0.002) and G allele ( p = 0.009) had conferred significant risk for complete remission failure. Although the log rank test was not significant, survival analysis had shown a trend where BCL2-938CA genotype, and BAX-248GG had reduced median disease-free survival (DFS) of 9 and 10 months, respectively. In conclusion, BCL2-938C>A and BAX-248G>A gene polymorphisms might contribute to the origin of AML. Moreover, influence of BAX-248GG genotype on CR and DFS rate suggests that the BAX-248G>A polymorphism can serve as marker for poor prognosis in AML. [ABSTRACT FROM AUTHOR]

Purpose: In adult differentiated thyroid cancer (DTC) patients, successful ablation and the number of I therapies needed carry a prognostic significance. The goal was to assess the prognosis of DTC in children and adolescents treated in our centre in relation to the number of treatments needed and to establish the determinants of both complete remission (CR) and successful ablation. Methods: Seventy-six DTC patients <21 years of age at diagnosis were included. Recurrence and death rates, rates of CR (=negative stimulated thyroglobulin, negative neck ultrasound and negative I whole-body scintigraphy) and successful ablation (=CR after initial I therapy) were studied. Results: No patients died of DTC. Seven patients were treated by surgery alone and did not show signs of recurrence during follow-up. Of the 69 patients also treated with I therapy, 47 patients achieved CR, 25 of whom had successful ablation. In multivariate analysis, female gender and the absence of distant metastases were independent determinants of a higher CR rate. Female gender, lower T stage and higher I activity (successful ablation, median activity 3.1 GBq, unsuccessful ablation 2.6 GBq) were determinants of a higher rate of successful ablation. After I therapy no patient showed recurrence after reaching CR or disease progression if CR was not reached. Conclusion: In our paediatric DTC population prognosis is extremely good with no deaths or recurrences occurring regardless of the number of I therapies needed or whether CR was reached. The determinants of CR and successful ablation can be used to optimize the chance of therapy success. [ABSTRACT FROM AUTHOR]

The clinical course of Behcet's disease (BD) as a multisystemic disorder with a remitting-relapsing nature is insufficiently explored. As complete remission should be aimed in all inflammatory diseases, we investigated the frequency of complete remission in patients with BD followed in long-term, routine practice. In this retrospective study, 258 patients with BD who were regularly followed in outpatient clinics were assessed. The demographic and clinical data for active organ manifestations and treatment protocols were evaluated, and 'complete remission' for this study was defined as no sign of any disease manifestation in the current visit and the preceding month. Two hundred fifty-eight patients with BD (F/M 130/128, mean age 41.1 ± 11.5 years) were included to the study. Mucocutaneous disease was present in 48.4 % ( n = 125). Mean visit number was 6.8 ± 2.7, and mean follow-up duration was 45.8 ± 36.5 months. Patients were clinically active in 67.2 % ( n = 1,182) of the total visits ( n = 1,757), which increased to 75.6 % (68.1-90.3) when the month preceding the visit was also included. The most common active manifestation was oral ulcers (39.4-63.2 %) followed by other mucocutaneous manifestations and musculoskeletal involvement. When multivariate analysis was performed, oral ulcers, which are the main cause of the clinical activity, negatively correlated with immunosuppressive treatments ( β = −0.356, p < 0.000) and age ( β = −0.183, p = 0.04). It is fairly difficult to achieve complete remission in BD with current therapeutic regimens. The reluctance of the clinician to be aggressive for some BD manifestations with low morbidity, such as mucocutaneous lesions and arthritis, might be influencing the continuous, low-disease activity state, especially due to oral ulcers, in BD patients. [ABSTRACT FROM AUTHOR]

Background: In recent years, tonsillectomy and steroid pulse (TSP) therapy have been widely performed in Japan. However, there is no consensus about the treatment protocol and indication. Methods: In this retrospective analysis, we compared patients who received tonsillectomy plus intermittent steroid pulse (SP) therapy three times in 6 months (ISP group, n = 44) with patients who received tonsillectomy plus 3 weeks of consecutive SP therapy (CSP group, n = 46) within 1 year after renal biopsy. These two different protocols were performed at two different institutions. We analyzed the clinical and histological background and clinical remission (CR), defined as disappearance of urine abnormalities at 18 months after starting treatment. Results: Before treatment, there was no significant difference in the clinical findings except for sex between the two groups. In ISP group and CSP group, mean estimated glomerular filtration rate was 82.1 ± 20.9 and 85.9 ± 19.1 ml/min/1.73 m, median proteinuria was 0.55 and 0.56 g/day, and median urinary red blood cells were 20 (10-20) and 20 (6-30)/high power filed. The histological (H) grade was lower in the CSP than the ISP group ( p = 0.022). The remission rate of proteinuria, hematuria, and rate of CR by the Kaplan-Meier method and logrank test were significantly higher in the CSP group than in the ISP group (CSP vs. ISP group; proteinuria: 97.8 vs. 77.3 %, p < 0.001, hematuria: 97.8 vs. 75.0 %, p = 0.005, CR: 95.6 vs. 63.6 %, p < 0.001). In the Cox proportional hazard model (forced entry), SP protocol and proteinuria before treatment were significantly associated with CR [SP protocol: hazard ratio (HR) 2.50, 95 % confidence interval (CI) 1.46-4.30, p = 0.001, proteinuria: HR 0.81, 95 % CI 0.68-0.96, p = 0.013)]. However H-grade was associated with remission of proteinuria (H-grade: hazard ratio (HR) 0.56, 95 % confidence interval (CI) 0.37-0.85, p = 0.006), and this result meant histological bias affected the remission of proteinuria. Conclusions: The difference of the protocol of TSP therapy may have some effect on the CR of IgAN, though the histological bias was observed in this study. The appropriate protocol and indication of TSP therapy must be analyzed and determined in the randomized controlled trial. [ABSTRACT FROM AUTHOR]

Bortezomib (bort)-dexamethasone (dex) is an effective therapy for relapsed/refractory (R/R) multiple myeloma (MM). This retrospective study investigated the combination of bort (1.3 mg/m on days 1, 4, 8, and 11 every 3 weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment in 85 patients with R/R MM after prior autologous stem cell transplantation or conventional chemotherapy. The median number of prior lines of therapy was 2. Eighty-seven percent of the patients had received immunomodulatory drugs included in some line of therapy before bort-dex. The median number of bort-dex cycles was 6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the patients achieved at least partial response, including 19 % CR and 35 % achieved at least very good partial response. Median durations of response, time to next therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively. The most relevant adverse event was peripheral neuropathy, which occurred in 78 % of the patients (grade II, 38 %; grade III, 21 %) and led to treatment discontinuation in 6 %. With a median follow up of 22 months, median time to progression, progression-free survival (PFS) and overall survival (OS) were 8.9, 8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was an effective salvage treatment for MM patients, particularly for those in first relapse. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of ulcerative colitis with drugs during pregnancy potentially may harm the mother and the unborn child. Granulocytapheresis depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested in the safety and efficacy of granulocytapheresis in patients who had ulcerative colitis flare up during pregnancy. Methods: Three pregnant cases with active ulcerative colitis received Adacolumn granulocytapheresis, up to 10 sessions within 3-6 weeks. Case 1: a 33-year-old woman with left-sided colitis and bloody diarrhoea 7-9 times/day showed loss of mucosal vascular patterns, and contact bleeding from the rectum to the sigmoid colon. Case 2: a 36-year-old woman with pancolitis and bloody diarrhoea 6-8 times/day had loss of mucosal vascular patterns and pus from the rectum to the sigmoid colon. Case 3: a 36-year-old woman with pancolitis and diarrhoea 4-5 times/day (first episode) had erosions and pus in the mucosa from the rectum to the transverse colon. Results: Colitis flare was in weeks 5, 13 and 22 of pregnancy in cases 1, 2, 3, respectively. The corresponding granulocytapheresis sessions were 5, 7, and 10, reflecting an increasing trend with the pregnancy week. Patients 1 and 2 achieved complete remission, patient 3 achieved clinical remission. Conclusion: In these three cases with active ulcerative colitis during pregnancy, granulocytapheresis as a non-pharmacologic treatment was effective and safe. In case 3 that did not respond well to the initial granulocytapheresis sessions, a moderate dose of prednisolone enhanced the efficacy of granulocytapheresis and tapering of prednisolone shortly after administration was not associated with relapse. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE). Methods: A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time. Results: Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥60 years; HR 1.531, P = 0.043), advanced Child-Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR. Conclusions: Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver. [ABSTRACT FROM AUTHOR]

This is the first case report of gastric plasmacytoma associated with ' Candidatus Helicobacter heilmannii' (' H. heilmannii') infection. The patient was a 40-year-old woman with epigastric discomfort. Upper gastrointestinal endoscopy demonstrated a white granular lesion on the wall of the gastric body. Histological studies showed numerous eosinophilic globules expanding the lamina propria mucosae. Immunohistochemically, the cells with these globules stained positive for CD138, CD79a, immunoglobulin (Ig) M, and kappa light chain, but negative for CD20, IgG, IgA, and lambda light chain. A diagnosis of plasmacytoma was made. Although a Helicobacter pylori infection was not detected, the patient received H. pylori eradication treatment. Two months after H. pylori eradication treatment, an upper gastrointestinal endoscopy showed a reduction of the white granular lesion. Eighteen months after eradication treatment, endoscopy, endoscopic ultrasonography and histological studies revealed complete remission of the lesion. No relapse has been documented 30 months after the initial diagnosis of plasmacytoma. Retrospectively, analysis of biopsy specimens removed before eradication treatment demonstrated that this patient had ' H. heilmannii' infection. Therefore, H. pylori eradication therapy should be considered as a potential first-line therapy for early-stage gastric plasmacytoma with or without H. pylori infection. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate clinical parameters that might predict complete remission (CR) following reinduction therapy in patients with acute myeloid leukemia (AML). We retrospectively analyzed outcomes in 142 patients who failed to achieve CR with standard anthracycline-plus-cytarabine induction chemotherapy (IND1) and who received the same regimen as a reduction therapy (IND2). The CR rate after reinduction was 54%. Multivariate analysis showed that the presence of peripheral blood (PB) blasts on the day of commencement of IND2 and ≥20% blasts in an interim BM sample taken during IND1 (C1-INT-BM) were independent risk factors for failure of remission. Our scoring system for prediction of CR after reinduction (CRAR score) included a favorable chromosome risk group, absence of PB blasts on the day of commencement of IND2, and ≤21% blasts in the C1-INT-BM. This scoring system predicted that the rates of CR in the four subgroups would be 92.1%, 68.9%, 29.5%, and 7.3%, respectively, in good agreement with observed CR rates. The CRAR scoring model might be associated with the possibility of achieving CR after reinduction, and may be helpful in choosing alternative strategy for AML patients refractory to standard induction chemotherapy, although further prospective validation is required. [ABSTRACT FROM AUTHOR]

Bortezomib-dexamethasone (Btz/Dex) is an active regimen in patients with multiple myeloma and has been used in few patients with amyloidosis. Here, we report a retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients with AL amyloidosis (AL). Eighteen patients (69%) received Btz/Dex as first-line treatment. Organs most frequently involved were kidneys (100%) and heart (35%); five patients (19%) had less than two organs involved. The overall response rate was 54% (14 of 26 patients), with eight patients (31%) achieving a hematologic complete remission (CR). All patients who reached a CR received Btz/Dex as first-line therapy. Median time to response was 7.5 weeks. Improvement in organ function was noticed in three patients (12%). Median progression-free survival (PFS) and overall survival (OS) was 5.0 and 18.7 months, respectively; in CR patients, however, median PFS and OS have not yet been reached. Toxicities were manageable, with hematological side effects being most common. No grade 3/4 neuropathy was observed. Our results confirm the activity of bortezomib/dexamethasone in patients with AL amyloidosis and suggest that patients achieving a CR have a marked benefit for survival. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphomas (PTCL) are rare and aggressive subtypes of non-Hodgkin's lymphoma. Compared to B cell lymphomas, the immunologic phenotype of PTCL portends a poorer prognosis, with the exception of anaplastic large cell lymphoma bearing the anaplastic lymphoma kinase protein. Patients with PTCL tend to present clinically in advanced disease states, show lower response rates to chemotherapy, and suffer from more frequent relapses and shorter remissions. The rarity of these lymphomas has made it difficult to carry out prospective, randomized trials delineating optimal treatments. Conventional and intensified chemotherapy have led to reasonable responses, but in many studies, frequent relapses. Consequently, high-dose chemotherapy and autologous stem cell transplantation (ASCT) have been actively studied in both the relapsed and upfront setting. In addition, the impact of disease status at transplantation is being investigated, though the optimal disease state at transplant is still a matter of debate, as is the timing of transplant. This article seeks to review the literature on the role of ASCT in PTCL, as well as to clarify what may be the optimal disease state in which to offer patients with PTCL autologous transplantation, if at all. [ABSTRACT FROM AUTHOR]

We report a case of 67-year-old Japanese woman with two types of metastasectomy for metachronous metastases of renal cell carcinoma (RCC). The initial nephrectomy for left RCC was performed in April 1977. The pathological diagnosis was clear cell carcinoma grade1-2, pT1b. In May 1996, computed tomography (CT) revealed a tumor in the upper pole of the remaining right kidney. The renal tumor was enucleated in June 1996. The histopathological diagnosis of the tumors was clear cell carcinoma. In December 1998, conventional B-mode ultrasound US detected solid tumors in the uncus, body, and tail of pancreas, and the patient underwent partial pancreatectomy, preserving the pancreatic head. Histologically, the tumor consisted of clear cell carcinoma. Eleven years following the second metastasectomy, patient was disease free without adjuvant therapy. [ABSTRACT FROM AUTHOR]

In advanced stages, cutaneous T cell lymphomas (CTCL) are associated with increased mortality from infections and also increased susceptibility to skin malignancies. In this study, we analyzed the complexity of the peripheral blood T cell repertoire with a sensitive b-variable (BV) complementarity-determining region 3 (CDR3) spectratyping analysis and flow cytometry in three-stage IV CTCL/Sezary syndrome patients who achieved complete clinical remission after therapy. The T cell repertoire of peripheral blood T cells before treatment was profoundly abnormal across multiple BV subfamilies. Following treatment, CDR3 spectratype patterns showed dramatic restoration of normal diversity and complexity. However, absolute CD4 counts across multiple BV families remained low for many months, even after identifiable circulating malignant T cell populations were eliminated. These data suggest that the diversity of the T cell repertoire can be recovered after successful treatment of even advanced CTCL. [ABSTRACT FROM AUTHOR]

Pathologic complete remission (CR) of rectal cancer after neoadjuvant chemoradiation therapy (CRT) is generally confirmed by routine hematoxylin and eosin (H&E) staining. The aim of this study was to identify residual rectal cancer cells in primary lesions of patients with pathologic CR by immunohistochemical staining for cytokeratin. The medical records of 358 rectal cancer patients who underwent neoadjuvant CRT prior to radical surgery between October 2002 and August 2007 were reviewed. The authors stained sections of resected specimens of 58 patients (15.9%; 42 males; mean age 54 years) who achieved pathologic CR (as determined originally by H&E staining) with H&E and performed immunohistochemistry (IHC) using monoclonal anti-cytokeratin antibody. These stained sections were reviewed for residual rectal cancer cells by a pathologist. Of the 58 patients that achieved CR by initial pathologic examinations, eight (13.8%) were found to contain tumor by cytokeratin IHC. H&E staining revealed that six of these were positive for cancer cells, but the remaining two were negative for residual rectal cancer cells. Through better identification of residual rectal cancer cells, cytokeratin IHC offers a means of improving staging accuracy and thus provides useful information for prognosis and treatment decisions for patients with rectal cancer who had a clinical CR after CRT. [ABSTRACT FROM AUTHOR]

In recent years, molecular-targeted agents have been used clinically to treat various malignant tumors. In May 2009, sorafenib (Nexavar®) was approved in Japan for “unresectable hepatocellular carcinoma (HCC)”, and was the first molecular-targeted agent for use in liver cancer. To date, sorafenib is the only molecular-targeted agent whose survival benefit has been demonstrated in two global phase III randomized controlled trials, and it has now been approved worldwide. Phase III clinical trials are now underway to compare other molecular-targeted agents with sorafenib as first-line treatment agents, and to evaluate other multi-kinase inhibitors of the vascular endothelial growth factor and platelet-derived growth factor receptors, as well as drugs targeting the epidermal growth factor receptor, insulin-like growth factor receptor, and mammalian target of rapamycin, in addition to other molecules targeting other components of the signal transduction pathways. This review outlines the main pathways involved in the development and progression of HCC and the agents that target these pathways. [ABSTRACT FROM AUTHOR]

Sorafenib has been shown to be active in AML patients with FLT3-ITD. However, the effect of sorafenib in AML patients with FLT-TKD has never been well determined. Moreover, acquisition of secondary FLT3 TKD mutations, mainly at D835 (D835F/H/V/Y), are recognized as the major mechanisms of resistance of AML patients with FLT3-ITD to sorafenib. It has been reported that sorafenib induced death of cells that expressed the FLT3-ITD or FLT3-D835G but not cells that expressed the FLT3-D835Y point mutant or wild-type FLT3 in vitro. Here, we report the successful complete remission induction by sorafenib monotherapy in a FLT3-D835Y-positive patient with refractory AML-M5 followed by allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

The aim of this prospective study was to investigate the feasibility of reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) in 37 adults with high-risk acute lymphoblastic leukemia (ALL) in first (n=30) or second (n=7) complete remission (CR). All patients were treated with fludarabine (150 mg/m2) and melphalan (140 mg/m2) followed by transplantation from matched sibling (n=27) or unrelated (n=10) donors. The indications for reduced-intensity conditioning allogeneic SCT (RIC-SCT) were as follows: (1) 50 years, 16 (43.2%) and (2) decreased organ function or active infections, 21 (56.8%). Graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitor (cyclosporine for sibling and tacrolimus for unrelated transplants) and methotrexate. The cumulative incidence of acute (grades II–IV) and chronic GVHD was 43.2 and 65.6%, respectively. After a median follow-up of 36 months for surviving transplants, the 3-year relapse, non-relapse mortality, disease-free survival and overall survival rates were 19.7, 17.7, 62.6 and 64.1%, respectively. Transplants in first CR showed better transplantation outcomes than those in second CR. The potential of antileukemic activity of chronic GVHD was also found. This study suggests that RIC-SCT is a potential therapeutic approach for adults with high-risk ALL in remission who are ineligible for myeloablative transplantation. [ABSTRACT FROM AUTHOR]

As recent chemotherapy regimens for metastatic colorectal cancer become more and more effective in a neoadjuvant setting before liver surgery, a “complete” clinical response is sometimes documented on imaging. Without operation though, metastatic recurrence is likely to commence within 12 months. Surgeons now face the problem to resect non-visualizable and non-palpable lesions. Computer-based virtual surgery planning can be used to fuse pre- and postchemotherapy computed tomography data to develop an operative strategy. This information is then intraoperatively transferred to the liver surface using an image-guided stereotactically navigated ultrasound dissector. This enables the surgeon to perform a resection that is otherwise not possible. During operation, detection of the lesion through palpation or ultrasound was impossible. After registering the virtual operation plan into the navigation system, the planned resection was performed without problems. Histopathologic workup showed vital tumor cells in the specimen. The new image-guided stereotactic navigation technique combined with virtual surgery planning can solve the surgeon’s dilemma and yield a successful operation. [ABSTRACT FROM AUTHOR]