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Non-myeloablative allogeneic hematopoietic stem cell transplantation for adults with relapsed and refractory mantle cell lymphoma: a single-center analysis in the rituximab era.

ABSTRACT: Relapsed and refractory (rel/ref) mantle cell lymphoma (MCL) portend a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potentially curative therapy in this setting. We analyzed the survival outcomes of 29 recipients of non-myeloablative allo-HSCT for rel/ref MCL, and studied possible prognostic factors in this setting. The cumulative incidences of disease progression and non-relapse mortality at 3 years were 28% (95% confidence interval (CI): 13-46%) and 29% (95% CI: 13-47%), respectively. The cumulative incidence of grade II-IV acute GvHD at days +100 and +180 was 34% (95% CI: 18-52%) and 45% (95% CI: 26-62%), respectively. With a median follow-up in survivors of 53 (range 24-83) months, the 3-year overall survival (OS) and PFS were 54% (95% CI: 38-76%) and 41% (95% CI: 26-64%), respectively. In vivo T-cell depletion with alemtuzumab (n=6) was associated with inferior 3-year PFS (0% vs 51%, P=0.007) and OS (17% vs 64%, P=0.014). Conversely, a second-line international prognostic index (sIPI) at transplantation equal to 0 (no risk factors) was associated with an improved 3-year PFS (52% vs 22%, P=0.020) and OS (71% vs 22%, P=0.006) compared with sIPI ?1. Performing an allo-HSCT before 2007 was associated with a decreased 3-year OS (25% vs 76%, P=0.015) but not with a significantly inferior PFS (17% vs 59%, P=0.058). In this single-center series, we report encouraging results with allo-HSCT for patients with rel/ref MCL. High alemtuzumab doses should probably be avoided in this context.

SUBMITTER: Mussetti A

PROVIDER: S-EPMC4935530 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Non-myeloablative allogeneic hematopoietic stem cell transplantation for adults with relapsed and refractory mantle cell lymphoma: a single-center analysis in the rituximab era.

Mussetti Alberto A Devlin Sean M SM Castro-Malaspina Hugo R HR Barker Juliet N JN Giralt Sergio A SA Zelenetz Andrew D AD Sauter Craig S CS Perales Miguel-Angel MA

Bone marrow transplantation 20150706 10

Relapsed and refractory (rel/ref) mantle cell lymphoma (MCL) portend a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potentially curative therapy in this setting. We analyzed the survival outcomes of 29 recipients of non-myeloablative allo-HSCT for rel/ref MCL, and studied possible prognostic factors in this setting. The cumulative incidences of disease progression and non-relapse mortality at 3 years were 28% (95% confidence interval (CI): ...[more]

PMID: 26146802

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Project description:BackgroundTemsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma.MethodsIn a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375 mg/m(2) per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967.Findings71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively).InterpretationmTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma.FundingNational Institutes of Health and the Predolin Foundation.

Dataset Information

Non-myeloablative allogeneic hematopoietic stem cell transplantation for adults with relapsed and refractory mantle cell lymphoma: a single-center analysis in the rituximab era.

Publications

Non-myeloablative allogeneic hematopoietic stem cell transplantation for adults with relapsed and refractory mantle cell lymphoma: a single-center analysis in the rituximab era.

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