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Background: This study analyzed the predictive value of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib. Methods: Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole‐side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI‐powered spatial TIL analyzer. Results: Twenty‐seven patients were included in the analysis. The best response was stable disease, and the median progression‐free survival (PFS) was 11.1 months (95% CI, 9.2–13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm2 (IQR, 8.3–73.0) and 180.4/mm2 (IQR, 69.6–342.8), respectively. Patients with stromal TIL density >342.5/mm2 exhibited longer PFS (p = 0.012). Conclusions: Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment. [ABSTRACT FROM AUTHOR]

Background: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2‐targeted agents. Docetaxel‐PM (polymeric micelle) is a low‐molecular‐weight, nontoxic, biodegradable, and docetaxel‐loaded micellar formulation. Trastuzumab‐pkrb is a biosimilar to trastuzumab. Methods: This was a multicenter, single‐arm, open‐label phase 2 study. Patients with HER2‐positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel‐PM (75 mg/m2) and trastuzumab‐pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). Results: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9–82.8) and a disease control rate of 93.0% (80.9–98.5). Median progression‐free survival, duration of response, and overall survival were 7.9 (6.3–9.5), 6.7 (5.1–8.4), and 23.3 (19.9–26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty‐eight (88.4%) patients experienced treatment‐related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. Conclusions: The combination of docetaxel‐PM and trastuzumab‐pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2‐positive advanced SDC. Plain Language Summary: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas.SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC.In this study, patients with HER2‐positive SDC were enrolled and treated with combination of docetaxel‐polymeric micelle and trastuzumab‐pkrb.Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression‐free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months. In this multicenter, single‐arm, phase 2 study, the authors evaluate efficacy and safety of docetaxel‐polymeric micelle and trastuzumab‐pkrb in patients with recurrent/metastatic human epidermal growth factor receptor 2 (HER2)‐positive salivary gland carcinoma. The data show that the combination therapy demonstrates promising antitumor activity with a manageable toxicity profile in patients with HER2 immunohistochemistry of 3+. [ABSTRACT FROM AUTHOR]

Aim: Long‐acting injectable antipsychotic agents (LAIs) including paliperidone palmitate (PP) have shown promising results in preventing relapse and rehospitalization in schizophrenia. This study aimed to ascertain the comparative real‐world effectiveness between the early and late administration of PP and oral formulations of risperidone and paliperidone (ORPs) in patients experiencing a first episode or relapse of schizophrenia. Methods: We identified patients with schizophrenia admitted to a psychiatric ward at least once and treated with ORPs or PP using the Korea National Insurance Claims Database. Patients were divided into three groups based on the clinical data: (1) patients treated with PP within 30 days of the initiation of treatment (early‐PP), (2) patients treated with PP after 30 days of the initiation of therapy (late‐PP) and (3) patients treated with only ORPs and not received PP (only‐ORP). The primary outcomes were determined as psychiatric rehospitalization during the entire duration of treatment after the first discharge. Results: A total of 3790 patients (1096 early‐PP, 799 late‐PP and 1895 only‐ORP) were finally included in the analysis. The mean of number and total length of rehospitalization stays during the entire duration in early‐PP group were significantly lower than those of late‐PP group and only‐ORP group (number: 2.32 stays/year, 3.24 stays/year and 4.23 stays/year, p <.001; total length: 50.34 days/year, 72.26 days/year and 105.14 days/year, p <.001). Conclusions: Early treatment with PP was associated with a greater reduction in psychiatric rehospitalization during the treatment period than late treatment with PP and ORP in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: The objective of the current study was to investigate the clinical activity of, safety of, and predictive biomarkers for afatinib, an irreversible pan‐ErbB kinase inhibitor, in patients with recurrent and/or metastatic esophageal squamous cell carcinoma (R/M‐ESCC). Methods: Patients with R/M‐ESCC that was refractory to platinum‐based chemotherapy were enrolled in the current multicenter, single‐arm, phase 2 study and received afatinib at a dose of 40 mg/day. The primary endpoint was the objective response rate. Secondary endpoints included progression‐free survival, overall survival, the disease control rate, and the safety profile. To identify predictive biomarkers, single‐nucleotide variations, short insertions/deletions, and somatic copy number alterations were assessed using whole‐exome sequencing and their associations with clinical outcomes were analyzed. Results: Among 49 enrolled patients, the objective response rate and disease control rate were 14.3% and 73.3%, respectively. With a median follow‐up of 6.6 months, the median progression‐free survival and overall survival were 3.4 months and 6.3 months, respectively. Treatment‐related adverse events were noted to have occurred in 33 patients (67.3%), with the majority being of grade 1 to 2 (adverse events were graded and recorded based on the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]). Whole‐exome sequencing demonstrated that the ESCC genomes of patients who demonstrated a response to afatinib were enriched with genomic alterations of TP53 and epidermal growth factor receptor (EGFR). As a predictive marker, a score derived from TP53 disruptive mutations and EGFR amplifications and/or missense mutations demonstrated a significant association with the response to afatinib. The score based on the mutational status of EGFR and TP53 achieved a performance of an area under the curve of 0.86 in predicting the sensitivity of afatinib. Conclusions: The results of the current study demonstrated that afatinib can confer modest clinical benefits with manageable toxicity in patients with platinum‐resistant R/M‐ESCC. Identification of TP53 alterations and EGFR amplifications may serve as predictive markers with which to identify patients with R/M‐ESCC who may benefit from afatinib. Lay Summary: Esophageal squamous cell carcinoma (ESCC) is a type of cancer with a dismal prognosis and very limited treatment options.The clinical efficacy of afatinib was evaluated in patients with recurrent and/or metastatic ESCC, with adverse events demonstrating the modest efficacy with manageable toxicity of this irreversible, pan‐ErbB kinase inhibitor. Whole‐exome sequencing analysis of 41 cases of ESCC further revealed that the patients harboring epidermal growth factor receptor (EGFR) amplifications and disruptive TP53 mutations are more likely to benefit from treatment with afatinib.The results of the current study have highlighted the clinical value of EGFR and TP53 as predictive biomarkers of platinum‐resistant recurrent and/or metastatic ESCC for afatinib sensitivity. Patients with recurrent and/or metastatic esophageal squamous cell carcinoma have a dismal prognosis with very limited treatment options. The results of the current phase 2 trial demonstrate that afatinib has modest efficacy and manageable toxicity, but the exploratory analyses using whole‐exome sequencing indicate that EGFR amplification and TP53 disruption might serve as predictive biomarkers for treatment with afatinib. [ABSTRACT FROM AUTHOR]

Objectives: Conventional guided bone regeneration (GBR) limits the amount of bone graft due to limited soft tissue expansion. We hypothesize that the use of tissue expander will successfully augment soft tissue prior to bone graft, allowing for sufficient amount of grafting which will lead to a more stable and effective vertical bone graft. The authors aimed to evaluate effectiveness of the novel self‐inflating tissue expander for vertical augmentation in terms of soft tissue expansion, clinical outcomes, and related complications. Material and methods: A prospective, multicenter, randomized controlled trial was performed on patients requiring vertical augmentation. For experimental group patients, the tissue expander was subperiosteally implanted and followed by a tunneling bone graft without full flap reflection. Control patients underwent conventional vertical GBR. Primary objectives were to evaluate the dimensional changes of soft tissue and radiographic vertical bone gain and retention. As a secondary outcome, clinical complications and thickness changes of expanded overlying tissue were assessed and analyzed. Results: Twenty‐three patients in each group were included. During a 4‐week expansion, two of the experimental group showed over‐expansion and one showed mucosal perforation associated with previous severe scars. The other patients showed uneventful expansion and mean tissue augmentation was 6.88 ± 1.64 mm vertically. Ultrasonographic measurements of overlying gingiva revealed no thinning after tissue expansion (p >.05). Significantly higher vertical bone gain was shown in the experimental group (5.12 ± 1.25 mm) compared with that in the control patients (4.22 ± 1.15 mm; p <.05). After a 6‐month retention period, the mean vertical bone measurement of the controls had decreased to 1.90 mm (55.0% reduction), which was a significantly greater decrease than that in the experimental group (mean 3.55 mm, 30.7% reduction; p <.05). Conclusion: Our results demonstrated the effectiveness of tissue expanders followed by tunneling bone graft for vertical augmentation; however, studies comparing the two techniques without tissue expanders are needed to elucidate the net effect of tissue expansion. [ABSTRACT FROM AUTHOR]

Aim: Antioxidants have been studied to be effective in improving embryo qualities from in vitro fertilization. L‐carnitine (LC) has been known to reduce reactive oxygen species and enhance adenosine triphosphate production, which contribute to the development of a high‐quality embryo. This is the first study to include both mouse and human subjects and aimed to evaluate whether LC supplementation in culture media has any beneficial effect on the development of the embryos, as well as its clinical outcomes. Methods: Mouse embryos were used as models in the animal studies for cell immunofluorescent staining evaluation. Inner cell mass and trophectoderm (TE) cells were counted and statistically analyzed between LC and control groups. For human studies, medical records of patients with infertility undergoing in vitro fertilization procedures from January to May 2017 were included and the embryos were divided into two groups at the two pronuclear stage. Statistical analysis was performed to compare the embryo status and clinical outcomes of the two groups. Results: In the animal study, the LC group showed significantly higher numbers of cells in the inner cell mass and trophectoderm, indicating better development. In the human studies, there were significantly higher numbers of good‐quality embryos on days 2, 3 and 5 in the LC group than in the control. The clinical outcomes, such as implantation, clinical pregnancy and ongoing pregnancy rates, were also higher in the LC group than in the control. Conclusion: LC supplementation in culture media improved human embryo quality and eventually achieved better pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objectives: In sacrococcygeal teratoma, the presence of high‐output cardiac failure resulting from arteriovenous shunting through the large tumor has been associated with an adverse outcome. The objective of this study was to determine whether the tumor size and cardiac biomarkers in cord blood can predict neonatal survival in sacrococcygeal teratoma. Methods: The study population consisted of 25 neonates with sacrococcygeal teratoma. Tumor size was calculated by the ellipsoid formula using dimensions measured by antenatal ultrasound ([length × width × depth in cm] × 0.52= volume in cm3). To adjust the gestational age, the tumor volume index (tumor volume/biparietal diameter) was adopted in the analysis. Cardiac biomarkers for heart failure (N‐terminal pro‐B‐type natriuretic peptide [NT‐pro‐BNP] and cardiac troponin T [cTnT]) were measured in cord blood taken at the time of delivery. Results: The rate of neonatal death was 24% (6 of 25). The cases that resulted in neonatal death had a higher tumor volume index and higher concentrations of NT‐pro‐BNP and cTnT than those with survival. A tumor volume index of greater than 60 cm3/cm, elevated NT‐pro‐BNP (>2000 pg/mL), and elevated cTnT (>0.08 ng/mL) had sensitivity of 100% for prediction of neonatal death. Conclusions: The tumor volume index and cord blood biomarkers for heart failure can be promising prognostic markers for neonatal survival in sacrococcygeal teratoma. [ABSTRACT FROM AUTHOR]

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone ( CTD) or daily thalidomide, melphalan, and prednisolone ( MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent ( TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. [ABSTRACT FROM AUTHOR]

Angelica gigas Nakai (AGN, Korean Dang-gui) is traditionally used for the treatment of various diseases including cancer. Here, we investigated multidrug-resistant phenotype-reversal activities of AGN and its compounds (decursin, ferulic acid, and nodakenin) in doxorubicin-resistant NCI/ADR-RES ovarian cancer cells. Our results showed that a combination of doxorubicin with either AGN or decursin inhibited a proliferation of NCI/ADR-RES cells. These combinations increased the number of cells at sub-G1 phase when cells were stained with Annexin V-fluorescein isothiocyanate. We also found that these combinations activated caspase-9, caspase-8, and caspase-3 and increased cleaved PARP level. Moreover, an inhibition of P-glycoprotein expression by either AGN or decursin resulted in a reduction of its activity in NCI/ADR-RES cells. Therefore, our data demonstrate that decursin in AGN inhibits doxorubicin-resistant ovarian cancer cell proliferation and induces apoptosis in the presence of doxorubicin via blocking P-glycoprotein expression. Therefore, AGN would be a potentially novel treatment option for multidrug-resistant tumors by sensitizing to anticancer agents. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND The objective of this study was to evaluate the efficacy and safety of dovitinib in patients with adenoid cystic carcinoma (ACC). METHODS ACC patients with documented disease progression within the past 12 months were eligible. Patients received oral dovitinib (500 mg once daily for 5 consecutive days followed by a 2-day rest every week) until disease progression or unacceptable toxicities. The primary endpoint was the probability of 4-month progression-free survival (PFS). Metabolic response was evaluated with positron emission tomography (PET)/computed tomography (CT) scans performed at the baseline and after 8 weeks of treatment. RESULTS Between September 2011 and April 2013, 32 patients with metastatic and/or unresectable ACC were enrolled in this prospective, multicenter trial. The 4-month PFS probability was 80.4%, and the median PFS was 6.0 months (95% confidence interval, 4.4-7.6 months). Tumor shrinkage was observed in 22 patients (68.8%), and 1 patient had a confirmed partial response. The disease control rate was 96.9%. Among 26 patients with PET/CT scans both before and after treatment (at 8 weeks), the metabolic activity of ACC was reduced in 13 patients (50.0%), and 5 patients (19.2%) achieved a metabolic partial response, which was defined as a ≥25% reduction in maximum standardized uptake values. Common grade 3 and 4 adverse events were asthenia (50.0%) and neutropenia (25.0%). CONCLUSIONS Dovitinib shows modest antitumor activity in the treatment of ACC. Cancer 2015;121:2612-2617. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

This study aimed to determine the objective response, toxicity, and clinical outcome of weekly rituximab consolidation after four cycles of R- CHOP21 in very elderly patients with DLBCL. A prospective, multi-institutional phase II trial was conducted on patients with previously untreated CD20+ DLBCL who were older than 70 yr. Patients were treated with four cycles of R- CHOP21 followed by weekly consolidation with rituximab (375mg/m2, four times infusion) ( NCT01181999). We also compared the clinical outcomes with an historical case-matched control group treated conventionally with six cycles of R- CHOP21. A total of 51 patients with newly diagnosed DLBCL were enrolled at 15 institutes between June 2010 and September 2013 . The median age was 76 yr (range: 70-89). Forty-one of the 51 patients completed the planned rituximab consolidation (R-consolidation). The overall response rate was 78.4%, comprising 74.5% with a complete response and 3.9% with a partial response. After a median follow-up of 20.3 months, 2-yr progression-free survival and overall survival were 63.9% and 68.7%, respectively. No serious toxicities were reported during rituximab consolidation. Weekly rituximab consolidation following four cycles of R- CHOP21 resulted in an acceptable response with high tolerability and could be a good compromise between efficacy and safety for elderly patients with DLBCL. [ABSTRACT FROM AUTHOR]

We evaluated the impact of functional polymorphisms in the vascular endothelial growth factor A ( VEGFA) and vascular endothelial growth factor 2 ( VEGFR2) genes on the survival of patients with diffuse large B cell lymphoma (DLBCL). Five potentially functional polymorphisms in the VEGFA (rs699947, rs2010963 and rs3025039) and VEGFR2 (rs1870377 and rs2305948) genes were assessed in 494 DLBCL patients treated with rituximab plus CHOP chemotherapy. The associations of genotype and haplotype with overall survival (OS) and progression-free survival (PFS) were analyzed. Of the five polymorphisms, VEGFR2 rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, patients with the AA + TA genotypes had significantly better OS ( P = 0.002) and PFS ( P = 0.004) than those with the TT genotype. The association between significantly better OS and the AA + TA genotypes was observed separately in patients with low (0-2; P = 0.035) and high (3-5; P = 0.043) International Prognostic Index scores. Multivariate analysis showed that, relative to the AA + TA genotypes, the TT genotype was an independent prognostic factor for poor OS (HR, 1.71; 95% CI, 1.21-2.43; P = 0.002) and PFS (HR, 1.57; 1.13-2.17; P = 0.004). Other independent significant predictors of survival in patients with DLBCL were International Prognostic Index score, age > 60 years, lactate dehydrogenase concentration >normal, extranodal disease >1 and presence of B symptoms. The VEGFR2 rs1870377 polymorphism might affect survival in patients with DLBCL, suggesting that angiogenesis might be related to poor survival in these patients. ( Cancer Sci 2012; 103: 497-503) [ABSTRACT FROM AUTHOR]

Stage IV marginal zone B-cell lymphomas (MZL) are detected in more than 25% of lymphoma patients. In this study, we conducted retrospective analyses of specific cases of stage IV MZL in order to assess their clinical features, as well as the treatments and prognoses of these cases. A total of 94 patients with histological diagnosis of stage IV-MZL from 17 different institutions in Korea were included. Multiple-mucosa-associated lymphoid tissue (MALT)-organs-involved MZL (M-MZL) was detected in 34 patients (36.2%). Bone-marrow-involved stage IV MZL (BM-MZL) was detected in 33 patients (35.1%). Median time to progression (TTP) was 2.4 years (95% CI, 1.9-2.9). Five- and 10-year overall survival rates were 84.5% and 79.8%, respectively. Patients with lymph node involvement in stage IV MZL appeared to have worse prognoses in TTP ( P = 0.015). Thirty-one patients were treated with a regimen including rituximab (CTx-R[+]), and 31 with a regimen that did not include rituximab (CTx-R[−]). The CTx-R(+) group showed better responses than the CTx-R(−) group (83.9% versus 54.8%, P = 0.026). However, no differences in TTP duration were detected ( P = 0.113). Stage IV MZL tend to follow an indolent disease course. Therefore, lymph node involvement is a more valuable prognostic factor for TTP. Rituximab appears to contribute to better responses, but not in cases of TTP. ( Cancer Sci 2010; 101: 2443-2447) [ABSTRACT FROM AUTHOR]

We previously showed that at least 5/mm3 hematopoietic progenitor cells (HPCs) could be used as a marker for initiating autologous blood stem cell collection (ABSCC). However, the timing of efficient ABSCC following mobilization is still to be determined. We conducted a prospective, randomized comparison of 5/mm3 versus50/mm3 peripheral blood (PB) HPCs as a surrogate marker to initiate efficient ABSCC. Forty-five consecutive patients, 26 with multiple myeloma (MM) and 19 with non-Hodgkin's lymphoma (NHL), were enrolled between October 2004 and October 2006. Chemotherapy was cyclophosphamide 4 g/m2 for MM and ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), with or without Rituximab, for NHL. Circulating HPCs were monitored daily with the Sysmex SE9000 automated hematology analyzer, and harvested CD34+ cells were counted by flow cytometry. ABSCC was initiated when HPC levels reached at least 5/mm3 (HPC5 group) or 50/mm3 (HPC50 group). The median number of harvested CD34+ cells was 15.0 × 106/kg and 21.0 × 106/kg in the HPC5 and HPC50 groups, respectively ( P = 0.23). Optimal collection (>5 × 106 CD34+ cells/kg) in a single session (day 1) was attained in 15 HPC5 patients (63%) and in 14 HPC50 patients (67%), and targeted collection of 5 × 106 CD34+ cells/kg was achieved in 100 and 95% of HPC5 and HPC50 patients, respectively ( P = 0.47), with a median number of 1 apheresis in both groups ( P = 0.58). There were no between group differences in optimal collection rate on day 1, median number of aphereses to achieve optimal collection, and overall optimal collection rate. HPC ≥ 5/mm3 and ≥50/mm3 are both reliable indices for the timing of ABSCC. J. Clin. Apheresis, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In the course of screening for novel anticancer compounds, CR229 (6-Bromo-2,3,4,9-tetrahydro-carbolin-1-one), a novel derivative of β-carbolin-1-one, was generated as a new scaffold candidate. For the first time, the authors demonstrate that CR229 inhibited the growth of HeLa cells by the induction of cell cycle arrest and apoptosis. Analysis of flow cytometry and western blots of HeLa cells treated with 2.5 µM CR229 revealed an appreciable cell cycle arrest in the G1, G2/M phase and apoptotic induction via the p53-dependent pathway. Furthermore, the release of cytochrome c from mitochondria was detected using confocal microscopy in HeLa cells treated with CR229. Accordingly, these data demonstrate that the anticancer activity of CR229 is associated with: (i) the down-regulation of cyclins and cyclin-dependent kinase; (ii) the induction of p53, p21, and p16; and (iii) the activation of caspase-3. ( Cancer Sci 2007; 98: 1402–1407) [ABSTRACT FROM AUTHOR]

Patients with transplant-ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28-day treatment cycle: pomalidomide (4 mg/day on days 1-21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64-86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7-9.0) and 18.48 months (95% CI, 9.4-27.6), respectively. The incidence rate of grade ≥ 3 non-hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment-associated infection is the main cause of morbidity and mortality., (© 2020 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (≥60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m(2) , days 1-4), cytarabine (1,000 mg/m(2) , days 1-4), and attenuated-dose idarubicin (5 mg/m(2) , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F = 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493)., (Copyright © 2012 Wiley Periodicals, Inc.)