Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation.

Allogeneic stem-cell transplantation (SCT) is a potentially curative therapy for lymphoid malignancies. Myeloablative conditioning is associated with high non-relapse mortality (NRM). Reduced-intensity condition (RIC) reduces NRM but relapse rate is increased. Novel regimens with intensive anti-malignancy activity but limited toxicity are of benefit. We evaluated outcomes of 144 lymphoma patients given allogeneic SCT with RIC consisting of fludarabine and treosulfan (FT, n = 50), intravenous-busulfan (FB2, n = 38) or melphalan (FM, n = 56). Sixty-nine patients (48%) had chemo-sensitive disease and 75 (52%) had chemo-refractory disease at SCT. The median follow-up is 39 months (4-149). Three-year survival was 67, 74 and 48% after FT, FB2 and FM, in chemo-sensitive disease (P = 0.14) and 34, 11 and 17% in chemo-refractory disease, respectively (P = 0.08). Three-year NRM was 24, 24 and 54% (P = 0.002), whereas relapse mortality was 22, 34 and 18%, respectively (P = 0.13). Multivariate analysis identified a high comorbidityscore, chemo-refractory disease and FM as associated with shortened survival. In conclusion, FB2 is associated with low NRM and good results in chemo-sensitive disease, but with higher relapse mortality rates. FM controls disease better, but with high NRM. FT probably balances these outcomes more optimally. It is as safe as FB2 and as cytoreductive as FM, resulting in improved outcome, mostly in advanced disease.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fludarabine and treosulfan compared with other reduced-intensity conditioning regimens for allogeneic stem cell transplantation in patients with lymphoid malignancies

Yerushalmi

Shem‐Tov

Danylesko

et al. 2015

“…16 In the recently reported LNH87-2 protocol for poor-risk aggressive NHL, there were no toxic deaths and no cases of late myelodysplasia among 125 autologous SCT patients receiving CBV with a BCNU dose of 300 mg/m. 2,42 Treatment-related toxicity was relatively low among our study patients. Pulmonary toxicity occurred in two patients (11%) with one death (6%) because of IP.…”

Section: Discussionmentioning

confidence: 96%

High-dose cyclophosphamide, BCNU, and VP-16 (CBV) conditioning before allogeneic stem cell transplantation for patients with non-Hodgkin's lymphoma

Rossi

Becker

Emmons

et al. 2003

Summary:Allogeneic stem cell transplantation (SCT) has been shown to be a curative therapy for some patients with non-Hodgkin's lymphoma (NHL). Total-body irradiation and high-dose cyclophosphamide combinations are the most established conditioning regimens used in this setting. We examined the efficacy and toxicity of cyclophosphamide, BCNU, and VP-16 (CBV) as a suitable chemotherapy-only regimen for NHL patients. In total, 18 patients, median age 42 years, with NHL were treated with CBV followed by allotransplant. Patients had received a median of two prior chemotherapy regimens. Median times to neutrophil and platelet recovery were 19 and 15 days, respectively. Interstitial pneumonitis occurred in one patient. There have been four relapses after a median follow-up of 39 months. Overall, there were four deaths, one because of relapse. The 2-year estimates of relapse-free and overall survival are 56 and 76%, respectively. CBV is a safe and an effective alternative to TBI-containing regimens before allogeneic SCT for NHL.

“…[48][49][50][51] Myeloablative regimens A NRM exceeding 50% was reported after myeloablative allo-HCT for relapsed HL. [52][53][54] Although many factors influence outcome, such as high number of prior therapies, hence late referrals for allografting, and suboptimal performance status, another reason for such a high mortality rate could be partly attributed to using myeloablative regimens in patients with comorbidities. Myeloablative conditioning studies were predominantly offered in the past when supportive care was less effective.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Managing Hodgkin lymphoma relapsing after autologous hematopoietic cell transplantation: a not-so-good cancer after all!

Kharfan‐Dabaja

Hamadani

Sibai

et al. 2014

Hodgkin lymphoma (HL) relapsing after an autologous hematopoietic cell transplant (HCT) poses a therapeutic challenge. In this setting, salvage chemotherapy (for example, gemcitabine-based, ifosfamide-containing and others) or immunotherapy (for example, brentuximab vedotin) is essential as a bridging-cytoreduction strategy to an allogeneic HCT. Myeloablative allogeneic hematopoietic cell transplantation in relapsed HL is associated with high rates of non-relapse mortality. In carefully selected patients with chemosensitive disease, allografting following lower-intensity conditioning regimens can provide durable disease control rates of about 25-35%. Promising early results with haploidentical and umbilical cord transplantation are noteworthy and are expanding this procedure to patients for whom HLA-matched related or unrelated donors are not available. Unfortunately, a significant number of HL patients relapsing after an autologous HCT are not candidates for allografting because of the presence of resistant disease, donor unavailability or comorbidities. Brentuximab vedotin is approved for HL relapsing after a prior autograft. Rituximab and bendamustine are also active in this setting, albeit with short durations of remission. Histone deacetylase inhibitors (for example, panobinostat, mocetinostat), mTOR inhibitors (for example, everolimus) and immunomodulatory agents (lenalidomide) have shown activity in phase II trials, but currently are not approved for this indication. Second autologous HCT are rarely performed but this approach should not be considered standard practice at this time. The need for effective agents for post autograft failures of HL largely remains unmet. Continuous efforts to ensure early referral of such patients for allogeneic HCT or investigational therapies are the key to improving outcomes of this not-so-good lymphoma.