Abstract

Background:Mantle cell lymphoma (MCL) is a rare subtype of non‐Hodgkin lymphoma. The standard of care for MCL, include regimens containing cytarabine, followed by consolidation with autologous stem cell transplantation (auto‐HSCT) and maintenance with rituximab. Allogeneic stem cell transplantation (allo‐HSCT) is usually reserved for patients who relapse after auto‐HSCT. The more used conditioning regimens in auto‐HSCT is BEAM and FEAM. The BEAM consisted of carmustine, etoposide, cytarabine and melphalan; however in the lasts year's carmustine is often substituted by fotemustine due to its difficult supplying. FEAM consisted of fotemustine, cytarabine, and melphalan.Aims:To describe incidence, conditioning regimens and outcomes in a cohort of MCL patients submitted to HSCT.Methods:We retrospectively reviewed LCM patients submitted to HSCT in our center from 2000 to 2018. Conditioning of auto‐ HSCT according BEAM and FEAM protocols. Conditioning of allo‐ HSCT with non‐myeloablative conditioning regimens (FluBu6 and FluBu8).Results:Fifty six MCL patients were submitted to HSCT, 78.6% male (n = 44), with a median age at HSCT of 56 (38–66) years. Fifty patients performed auto‐ HSCT with BEAM conditioning regimen (n = 29) and FEAM (n = 21). Six patients performed allo‐ HSCT.At the time of auto‐HSCT, 96 % of the patients (n = 48) had complete response (CR), with 85.7% (n = 44) submitted to HSCT in the first response. At the time of allo‐HSCT, 67 % of the patients (n = 4) had CR. Median inpatient stay during HSCT was 24(21–47) days, without differences between BEAM vs FEAM (24 vs 24; p = 0.812).Most patients were treated in first‐line with R‐HyperCVAD (73%; n = 41), followed by R‐CHOP (n = 7, 12.5%) and R‐CHOP / R‐DHAP (10.7; n = 6).Considering BEAM vs FEAM regimen, there were no differences in the incidence of oral mucositis grade 2 (62 vs 57%, p = 0.776), febrile neutropenia> 5 days (36 vs. 50%; p = 0.286), gastrointestinal toxicity (grade 2–3) 72 vs 52%, p = 0.232.The time until neutrophils>500/μL was 11 vs 12 days, p = 0.284 and up to platelets>20,000/μL was 14 vs 13, p = 0.596, with 11 vs 12; p = 0.284 days for engraftment criteria establishment. The median OS is higher in BEAM 169.5 vs 52.5 months; p = 0.005.Of the 23 patients (41%) who relapsed after auto‐HSCT, 78% (n = 18) were treated with subsequent regimen: 3 with cytarabine, 11 with regimen including anthracycline but not cytarabine, 2 with ibrutinib, 1 with azacitidine and 1 with regimen palliative.HSCT in the first response was associated with lower mortality (OS median 112.7 vs 23.7 months; HR 0.22, p = 0.003).The number of CD34 + cells infused was not associated with OS impact (HR 1.22; p = 0.409).Previous treatment with regimens including cytarabine (Hyper‐CVAD and R‐DHAP) were associated with higher OS, although not statistically significant (HR 0.44, p = 0.089).No influence of Ann Arbor stage (p = 0.148) or MIPI score (p = 0.151) at diagnosis in OS.The median PFS after auto‐HSCT was 70.7 months, without differences between BEAM vs FEAM (p = 0.831)Summary/Conclusion:Our real life results claim, BEAM regimen should remain the regimen of choice, in patients with mantle lymphoma based on higher OS in BEAM than the FEAM (169.5 vs 52.5 months, HR 0.21, p = 0.005), even after inclusion in a multivariate model (HR 0.20, p = 0.016). This value was maintained when evaluating its impact on HRT (HR 0.06, p = 0.017), even after multivariate analysis for mucositis, febrile neutropenia and engraftment time (HR 0.03; p = 0.014.) Although PFS in our study are similar. Prospective studies are needed to confirm these findings.

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