Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission

Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. Results: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. Conclusions: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment

The Timing of Granulocyte Colony-Stimulating Factor in Hematopoietic Stem Cell Transplant in the Pandemic

Granulocyte-colony stimulating factors (G-CSF) are used to shorten the duration of neutropenia after hematopoietic cell transplantation (HCT). However, there is no consensus on which days treatment should be started post-transplantation during the COVID-19 pandemic. In this study, we looked at the influence of G-CSF on clinical outcomes on the fifth (G-CSFd5) and tenth (G-CSFd10) days following allo-HCT. Our study includes the data of 60 patients (G-CSFd5, n=28 vs G-CSFd10, n=32) who underwent HCT with the diagnosis of acute lymphoblastic leukemia (ALL) between 2015 and 2022. Primary outcome is the effect of G-CSF on hospital stay. Secondary outcomes are the development and duration of febrile neutropenia (FEN), neutrophil engraftment (NE), platelet engraftment (PE), engra ftment syndrome (ES), acute graft versus host disease (aGVHD), cytomegalovirus (CMV) viremia, and effects on antimicrobial use . Length of hospital stay, 34.5 days vs. 30 days (p=0.19); median NE, 13.85 vs 15.03 days (p=0.007); median PE, 15.5 vs 12 days (p =0.12); ES, 28.5% vs 12.5% (p=0.12); FEN, 85.7% vs 84.3% (p=0.88); aGVHD, 39.2% vs 40.6% (p=0.92); were observed for G-CSFd5 and G-CSFd10, respectively. Although starting G-CSF in the early period after allo-HCT shortened the duration of NE, positive effects on clinical outcomes were not observed. On the contrary, the frequency of ES increased in the group that received GCSF early

Is the Optimal Timing First Complete Remission for Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma?

Aim:Outcome for most patients with peripheral T cell lymphomas (PTCLs) is poor, with low response rates and short durations of remission. We aim to analyze the outcome of PTCL patients who underwent autologous stem cell transplantation (ASCT) at our center and we researched whether first complete remission (CR) was the optimal timing for ASCT in patients with PTCL.Materials and Methods:The data of PTCL patients who underwent ASCT between January 2010 and December 2020 at our center were retrospectively analyzed.Results:Twenty-five patients with PTCL underwent ASCT. The median ASCT age was 44 years (range: 19-68). 68% of the patients were performed upfront ASCT after the first CR; 32% of the patients underwent ASCT after relapse or refractory (R/R) disease. The median follow-up time from diagnosis was 40 months (13-144 months). The five-year PFS and OS were 50.8% and 55.7%, respectively. Five-year OS was 82.4% in the up-front ASCT group, while the five-year OS was 15.6% in the R/R patients (p=0.019). The median OS was 25 months [95% confidence interval (CI): 0-50.4] in patients who had CR2, while it was 13 months (95% CI: 0-35) in patients who had PR before ASCT (p=0.03). According to subtypes of PTCL, OS and PFS were not statistically different in all groups (p=0.96 and p=0.79, respectively). Conclusion:Even the prognosis is poor in patients with PTCL, Overall survival was significantly longer among the upfront ASCT group. Patients should be consolidated with ASCT in the first CR, and relapse should not be waited to perform ASCT

Clinical findings and immunophenotypic profile of plasma cell leukemia: a retrospective study in a comprehensive cancer center in Turkey

Plasma cell leukemia (PCL) is a rare (1-2 %) aggressive plasma cell dyscrasia (PCD) with a poor prognosis and characterized by the presence of more than 20% circulating plasma cells (PCs). Multicolor Flowcytometry is used for differentiating PCs in PCL. In this study, we aimed to compare the clinical, laboratory findings and immunophenotypic profiles of patients with PCL. A total of 512 patients were investigated for PCD in our hospital between 2011-2019. The immunophenotypic profile (including, CD27, CD28, CD38, CD138, CD45, CD117, CD19, CD20, CD56, CD33, CD81, and ckappa /clambda,) were evaluated retrospectively. The clinical findings, pathology reports, immunofixation electrophoresis and MFC results of three patients with PCL were reevaluated using 6 color multiparametric flow cytometry (MFC). Only three patients were diagnosed as PCL. PCs population defined by the co-expression of CD38 and CD138 was observed as 50%, 53%, 60%, respectively. Expression of each CD56, CD117, CD20, CD45 was seen in individual cases. CD19 was negative in all cases. Cytoplasmic kappa light chain expression was detected only in one case. Two of the cases were primary and the other was secondary PCL. Bortezomib-based treatment was initiated. Overall survival of primary PCL cases were 24 months and 6 months, whereas secondary PCL was four months. Co-expression of CD38 and CD138 in identifying PCs with MFC may be considered the best combination and leads to early diagnosis within hours and appropriate treatment in patients with PCL. [Med-Science 2021; 10(2.000): 455-61

OUTCOME OF ALLOGENEIC STEM CELL TRANSPLANTATION WITH ACTIVE DISEASE IN ACUTE MYELOID LEUKEMIA

Introduction: Despite multiple lines of chemotherapy, some patients with acute myeloid leukemia (AML) can not achieve remission. The prognosis of these patients is quite poor and they should be evaluated for clinical trials, otherwise myeloablative conditioning regimens followed by allogeneic stem cell transplantation (Allo-SCT) should be performed to over come the active disease which is resistant to conventional doses and as it is the only curative option. Method: In this study, we evaluated the outcome of AML patients who underwent Allo-SCT with active disease in our center retrospectively. Results: A total of 161 AML patients underwent Allo-SCT between December 2009 and November 2018 at our center. 130 of them underwent Allo-SCT in complete remission while 31 of 161 had to undergo Allo-SCT with active disease due to refractoriness to salvage therapies. The median overall survival (OS) was7.9±2.8 months. 6-month OS was 25% and 1-year OS was only 6%. Progression-free survival (PFS) was 3.53±1.1 months. The transplant-related mortality rate was12.8%. Conclusion: OS and PFS are short in patients who undergo Allo-SCT with active diseases on oveltreatment approaches and targeted therapies should be developed to overcome active disease that are refractory to conventional chemotherapies