Outcome following Reduced-Intensity Allogeneic Stem Cell Transplantation (RIC AlloSCT) for relapsed and refractory mantle cell lymphoma (MCL): a study of the British Society for Blood and Marrow Transplantation.

Reduced-intensity allogeneic stem cell transplantation (RIC-AlloSCT) is being increasingly considered for patients with aggressive lymphoma, but limited evidence exists in mantle cell lymphoma (MCL). We report a retrospective study of transplant outcomes of RIC-AlloSCT for MCL in 70 patients (median age, 48 years, range: 30-67 years), with 57 patients receiving an Alemtuzumab-containing regimen. Thirty-four percent of patients had received a prior autologous stem cell transplant. The 1- and 5-year nonrelapse mortality (NRM) was 18% (95% confidence interval [CI] 10-27) and 21% (95% CI 12-31), respectively. The incidence of severe (grade III and IV) acute graft-versus-host disease (aGVHD) was 10%, and the 5-year incidence of chronic GVHD (cGVHD) was 61%. The cumulative relapse risk was 65% (95% CI 48-77) at 5 years, significantly affected by disease status at transplant (P = .0495), specifically the presence of chemosensitive disease (P = .0364). Fifteen of 18 relapsed patients received donor lymphocyte infustion (DLI) (n = 14) or a second RIC-AlloSCT (n = 1), with 11 of 15 currently in CR. The 5-year overall survival (OS) and progression-free survival (PFS) were 37% (95% CI 25%-56%) and 14% (95% CI 6%-34%), respectively. Age at transplantation and having <2 prior lines of therapy influenced the OS, whereas having <2 prior lines of therapy was the only factor to influence PFS. The use of Alemtuzumab in the conditioning was associated with an improved OS at 3 years (P = .0271). RIC-AlloSCT is a potential treatment modality for aggressive MCL. For patients relapsing post-AlloSCT, the disease is salvageable with DLI. The timing of RIC-AlloSCT should be explored in prospective studies to establish the optimal role in the management of this aggressive lymphoma.

Complete molecular responses are achieved after reduced intensity stem cell transplantation and donor lymphocyte infusion in chronic myeloid leukemia.

Patients with newly diagnosed chronic phase chronic myeloid leukemia were treated with imatinib mesylate (IM) for 6 to 12 months to establish disease control, before reduced intensity stem cell transplantation (RISCT). Escalating doses of donor lymphocyte infusions were given from 6 months after transplantation to eradicate residual disease. A total of 18 patients entered the study and 15 received RISCT (median follow-up, 31 months). RISCT was well tolerated with rapid engraftment, short inpatient stays, and few readmissions. Viral reactivation was common, although extensive graft-versus-host disease occurred infrequently. Donor lymphocyte infusions were given as part of the RISCT protocol in 13 of 15 patients. BCR-ABL transcripts continued to decrease after RISCT, and 8 (53%) patients achieved sustained undetectable levels. All patients are currently off IM. Although IM is now established as first-line therapy for chronic phase chronic myeloid leukemia, this protocol is a safe, well-tolerated, and effective strategy in these patients. This study is registered at http://www.controlled-trials.com as ISRCTN86187144.

The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation.

We describe the toxicity and efficacy of donor lymphocyte infusions (DLIs) given to 81 patients (median age, 50 years) after reduced-intensity conditioning (RIC) transplantations performed at 16 centers in the United Kingdom. The diseases treated included non-Hodgkin lymphoma (NHL; n = 29), chronic myeloid leukemia (CML; n = 12), myeloma (n = 11), acute myeloid leukemia (AML; n = 10), and chronic lymphocytic leukemia (CLL; n = 9). Eighty-eight percent received stem cells from sibling donors. The patients received 130 infusions (median, 1; range, 1-4). Indications for DLI were unsatisfactory response/disease progression in 51 patients, mixed chimerism in 18, preemptive in 10, and other in 2. Graft hypoplasia was uncommon (11%). Grade II to IV graft-versus-host disease (GVHD) occurred in 23 of 81 patients (28%) and limited and extensive chronic GVHD in 5 of 69 and 18 of 69 evaluable patients (total incidence 33%). Conversion from mixed to full donor chimerism occurred in 19 of 55 evaluable patients (35%) at a median of 48 days after the DLI; partial responses occurred in 6 patients (total response rate 45%). Eighteen of 51 (35%) patients with measurable disease after stem cell transplantation had a complete response (2 molecular), and 5 a partial response (total response rate 45%). Eleven of 17 evaluable complete responders had full donor chimerism. Eight of 13 patients with follicular NHL had complete responses as did 4 of 12 patients with CML. Clinical and chimeric responses correlated strongly with acute and chronic GVHD. Forty-seven patients (58%) survive at a median of 508 days after transplantation (range, 155-1171 days) with a median Karnofsky score of 90. Thirty-four patients (42%) died at a median of 211 days after transplantation with the major causes being progressive disease (26%) and GVHD (9%). Further systematic studies are required to determine the efficacy and optimum use of DLI for patients with each disease treated by nonmyeloablative stem cell transplantation.