Allogeneic transplantation after reduced intensity conditioning with fludarabine/cyclophosphamide is feasible and effective for highly resistant indolent and aggressive lymphoid malignancies

Wondergem M., Dijkstra F., Visser O., Zweegman S., Ossenkoppele G., Witte B., Janssen J.

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Abstract

Background: Allogeneic stem cell transplantation (alloSCT) is a potentially curative treatment strategy for relapsed lymphoid malignancies. Aims: We studied outcomes of 54 patients with relapsed or refractory indolent as well as aggressive lymphoid malignancies, who received alloSCT after reduced intensity conditioning in our center. Although the patient group reported here is heterogeneous as to lymphoma type and previous treatments, all patients had at least stable disease before transplantation and received the same conditioning regimen consisting of fludarabine and cyclophosphamide. Methods: All patients received alloSCT after reduced-intensity conditioning with fludarabine and cyclophosphamide between July 2001 and November 2010 at the VU University medical center. AlloSCT was applied because of relapse after autologous stem cell transplantation (autoSCT) or because no further therapy was expected to lead to cure or a meaningful remission. The conditioning regimen consisted of fludarabine 25 mg/m2 i.v. and cyclophosphamide 500 mg/m2 i.v., both from day -7 until -3. Patients received an unmanipulated peripheral blood stem cell graft, targeting at a minimum of 4.0x106 CD34+ cells/kg patient body weight at day 0. Data were collected using retrospective chart review and analyzed using the SPSS statistical package (version 20.0). Overall survival (OS) and event free survival (EFS) were estimated using the Kaplan Meier method and compared using the log-rank test. Results: A total of 54 patients were treated between July 2001 and November 2010. Median follow up of all patients alive at last follow up is 67 months (range 19-130 months). Patients were diagnosed with B-CLL (n=13), indolent B cell lymphoma (n=12), aggressive lymphoma (n=13) and 16 had DLBCL classified as transformation of indolent lymphoma. Thirty-two patients (59%) previously received rituximab. Immediately (in the first 0-3months) after conditioning and transplant, remission status had improved in 21 patients, all without donor lymphocyte infusions (DLI). During follow up six additional patients achieved CR without further therapy. Four patients relapsed within 6 months, and seven relapsed more than 6 months after transplant (range 9-58 months). Five patients required DLI during follow-up, all because of disease persistence or progression, resulting in remission in four patients. Analysis per disease category revealed a 4-year OS for B-CLL of 46% (95%CI: 19-73%), 83% for indolent Bcell lymphoma (95%CI: 62-100%), 69% for aggressive lymphoma (95% CI:44- 94%) and 74% for transformed lymphoma (95%CI: 52-96%). (NS, P=0.28, see Figure 1). Four-year EFS was 46%, 75%, 55% and 67% respectively (95%CI: 19-73%, 51-100%, 24-87% and 44-91% respectively, NS, P=0.54). OS was not significantly different between patients with (n=16) and without (n=38) previous autologous stem cell transplantation. One year non relapse mortality was 11%, increasing to 16% after two years. (95%CI: 2.2-20% and 5.7-26% respectively) Summary / Conclusion: Reduced intensity conditioning with fludarabine cyclophosphamide is feasible with acceptable toxicity and effective for both highly resistant indolent and aggressive lymphatic malignancies, even after previous autoSCT. Due to the excellent anti-B-cell/lymphoma activity, fludarabine- cyclophosphamide decreases tumor load during alloSCT, gaining time for the development of a graft versus lymphoma effect, which was also apparent after DLI. (Figure Presented).
Original languageEnglish
Pages (from-to)655
Number of pages1
JournalHaematologica
Volume98
Publication statusPublished - 2013

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