Allogeneic hematopoietic stem cell transplantation should be in preference to conventional chemotherapy as post-remission treatment for adults with lymphoblastic lymphoma.
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ABSTRACT:
SUBMITTER: Yang L
PROVIDER: S-EPMC6173686 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
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Allogeneic hematopoietic stem cell transplantation should be in preference to conventional chemotherapy as post-remission treatment for adults with lymphoblastic lymphoma.
Yang Luxin L Tan Yamin Y Shi Jimin J Zhao Yanmin Y Zhu Yuanyuan Y Hu Yongxian Y Pan Wenjue W Ye Yishan Y He Jingsong J Zheng Weiyan W Sun Jie J Cai Zhen Z Huang He H Luo Yi Y
Bone marrow transplantation 20180430 10
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| S-EPMC10906479 | biostudies-literature
Project description:To study the prognostic factors of adult patients with T-lymphoblastic lymphoma (T-LBL) and to evaluate therapeutic effects of acute lymphoblastic leukemia (ALL)-type chemotherapy in combination with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients who achieved overall response (OR) with first line ALL-type chemotherapy.This was a retrospective study of 59 adult patients with T-LBL treated with hyper-fractionated administration of cyclophosphamide, vincristine, doxorubicin and dexamethasone/methotrexate (hyper-CVAD/MA) chemotherapy alone or in combination with allo-HSCT between June 2008 and October 2015. Complete response (CR) and OR rates were evaluated after the initial chemotherapy. Clinical characteristics and the risk factors associated with prognosis and overall survival (OS) were analyzed in all patients and the effects of allo-HSCT on OS were evaluated in patients who had achieved OR after initial chemotherapy.Forty-eight patients (81.4%) achieved OR by hyper-CVAD chemotherapy, among which, 22 patients (45.8%) further received allo-HSCT. The median follow-up was 31.5 months, ranging from 11 to 97 months. The 3-year OS and progression-free survival (PFS) were 45.7% and 45.0% for patients who achieved OR after chemotherapy and both 0 for patients who did not achieve OR (both P?<?.001). Three year OS and PFS were higher in patients who received chemotherapy + allo-HSCT than in patients who received chemotherapy alone (3-year OS: 72.8% vs 17.5%, P?=?.008; PFS: 65.1% vs 27.8%, P?=?0.007). Shorter survival was independently associated with elevated lactic dehydrogenase (LDH), Ki-67?75%, pleural effusion and no OR (all P?<?.05) in all patients. But shorter survival was only associated with elevated LDH level, leukocytosis (>10 G/L), and chemotherapy alone in patients who achieved OR (all P?<?.05).The mid-term outcomes of adult patients with T-LBL are associated with response to chemotherapy (in all patients) and performance of allo-HSCT (in patients who achieved OR). Allo-HSCT could be a feasible and effective consolidation therapy for adult T-LBL.
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| S-EPMC11231304 | biostudies-literature
Project description:Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P = .021), age >35 years (HR, 1.55; P = .025), and disease status at HCT (HR, 1.98; P = .005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure.
| S-EPMC5549947 | biostudies-literature
Project description:RationaleAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for hematological malignancies. Common complications are opportunistic infections and graft-versus-host disease (GVHD). Cytomegalovirus (CMV) is one of the most common causes of opportunistic infections.Patient concernsA 30-year-old male was diagnosed with T-cell lymphoma after persistent cough and lymphadenopathy. Fever, abdominal pain, diarrhea, rash, and dyspnea occurred after HSCT.DiagnosisThe young man developed severe CMV infection with CMV detected in the bronchoalveolar lavage fluid and gastrointestinal tract.InterventionsIntravenous ganciclovir and high-dose glucocorticoids were administered after the patient was diagnosed with CMV pneumonia and enteritis.OutcomesAfter 3 weeks, the young man died from respiratory failure and infectious toxic shock caused by severe CMV infection.LessonsPatients after HSCT should be closely monitored CMV-DNA in blood and other specimen, and treated first if necessary, so as to avoid the occurrence of severe infections such as CMV gastroenteritis and pneumonia.
| S-EPMC6358403 | biostudies-literature
Project description:For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed using the following macroeconomic indicators as main effects: Gross national income per capita, health expenditure per capita, and Human Development Index (HDI). The outcome was overall survival at 100 days following transplantation. In each model, transplants performed within lower resourced environments were associated with inferior overall survival. In the model with the HDI as the main effect, transplants performed in the lowest HDI quartile (n = 697) were associated with increased hazard for mortality (hazard ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with transplants performed in the countries with the highest HDI quartile. This translated into an 11% survival difference at 100 days (77% for lowest HDI quartile versus 88% for all other quartiles). Country-level macroeconomic indices were associated with lower survival at 100 days after alloHCT for ALL. The reasons for this disparity require further investigation.
| S-EPMC6146070 | biostudies-literature
Project description:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered for patients with high-risk B-cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long-term follow-up data of patients who underwent allo-HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo-HSCT because of high-risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty-five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow-up duration was 18.6 months. The probability of 3-year progression-free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1-year non-relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft-versus-host disease (GVHD) were factors associated with inferior OS. The probability of 3-year OS in patients with diffuse large B-cell lymphoma who underwent allo-HSCT and allo-HSCT after ASCT was 40.2% and 25.2%, respectively. Allo-HSCT could be a salvage therapeutic option for relapsed or refractory B-cell lymphoma. Complete remission at the time of allo-HSCT and the presence of GVHD are independent variables for overall survival.
| S-EPMC10757116 | biostudies-literature
Project description:The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at www.clinicaltrials.gov as #NCT00896493.
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Project description:Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78% vs. 37%; p<0.01) and more with complex cytogenetics (44% vs. 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft-versus-host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] vs. 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% vs.11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] vs. 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% vs.11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T vs. the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% vs. 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% vs. 64.1%; p=0.63) and overall survival (OS; 70.2% vs. 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.
| S-EPMC8138447 | biostudies-literature
Project description:Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single-center phase 2 study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least 1 cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44 to 105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the only grade 4 adverse event (19%). Rates of cytokine release (5% G1) and neurotoxicity (5% G2) were minimal. The cumulative incidence of acute graft-versus-host disease (GVHD) grades 2 to 4 and 3 to 4 were 33% and 5%, respectively; 2 cases of mild (10%) and 1 case of moderate (5%) chronic GVHD were noted. With a median follow-up of 14.3 months, the 1-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) rates were 85%, 71%, and 0%, respectively. In a matched analysis with a contemporary cohort of 57 patients, we found no significant difference between groups regarding blinatumomab's efficacy. Correlative studies of baseline and posttreatment samples identified patients with specific T-cell profiles as "responders" or "nonresponders" to therapy. Responders had higher proportions of effector memory CD8 T-cell subsets. Nonresponders were T-cell deficient and expressed more inhibitory checkpoint molecules, including T-cell immunoglobulin and mucin domain 3 (TIM3). We found that blinatumomab postallogeneic HCT is feasible, and its benefit is dependent on the immune milieu at time of treatment. This paper is posted on ClinicalTrials.gov, study ID: NCT02807883.
| S-EPMC8952188 | biostudies-literature