Nonmyeloablative Stem Cell Transplantation Is an Effective Therapy for Refractory or Relapsed Hodgkin Lymphoma: Results of a Spanish Prospective Cooperative Protocol

Abstract

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.

Pretransplantation [18‐F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non‐Hodgkin lymphoma undergoing reduced‐intensity conditioning followed by allogeneic stem cell transplantation

“…24 Several groups have described the results from alloSCT after RIC in patients with recurrent and refractory HL; and, although the published studies are heterogeneous in terms of RIC protocols and the duration of follow-up, they indicate that disease status at the time of alloSCT influenced outcome in all series and that outcomes were favorable when patients developed recurrences >12 months after autologous SCT. 25 Peggs et al used an RIC regimen of fludarabine/melphalan and alemtuzumab and recorded a 4-year PFS rate of 67% and an OS rate of 100% in patients who were in CR or uncertain CR (CRu) at the time of transplantation. 3 Furthermore, Anderlini et al recently reported a 2-year PFS rate of 57% in patients who achieved CR/CRu before alloSCT using a similar RIC regimen without alemtuzumab.…”

Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma

“…5,6 Nevertheless, a substantial number of patients will also relapse after HDC and will require further therapy. In this setting, an allo-SCT folllowing reduced intensity conditioning or nonmyeloablative regimens (NMA) has been shown to be feasible [6][7][8][9][10][11][12][13][14] and superior in terms of survival and PFS, when compared with other therapeutic options. 15 The problem with an allo-SCT is that the majority of patients lack an identical sibling and no more than 50% of patients, searching the Registries for unrelated donors or cord blood units, undergo an allo-SCT (World Marrow Donor Association data, 2012 unpublished).…”

Tacrolimus and mycofenolate mofetil as GvHD prophylaxis following nonmyeloablative conditioning and unrelated hematopoietic SCT for adult patients with advanced hematologic diseases

“…[10][11][12][13]31,32 The long-term results observed in our patients who failed to achieve remission before NM conditioning are poor, with a corresponding 3-year OS probability of 20%, which is significantly lower than the 59% for patients treated in remission.…”