Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma.

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28-70) years with a followup time of 28.5 (3-164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18-0.67) and OS (HR 0.29; 95% CI 0.15-0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37-0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population.

Reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed multiple myeloma.

Despite recent advances, multiple myeloma (MM) remains incurable, and most patients eventually develop progressive disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a potentially curative option in 10%-20% of patients with relapsed or refractory disease. We evaluated the outcome of patients undergoing allo-HSCT with reduced-intensity conditioning (RIC) for relapsed and/or refractory MM at our institution. The study cohort included 51 patients with heavily pretreated, relapsed MM who underwent RIC allo-HSCT between 1996 and 2006. The median time from diagnosis to allo-HSCT was 34 months, and median follow-up in surviving patients was 27 months (range, 3-98 months). Cumulative transplantation-related mortality at 1 year was 25%. Progression-free survival (PFS) and overall survival (OS) at 2 years were 19% and 32%, respectively. The incidences of grade II-IV acute and chronic graft-versus-host disease were 27% and 47%, respectively. At the time of this analysis, 12 patients (24%) were alive, 7 of whom (14%) were in remission for up to 6 years after allo-HSCT. A lower beta2 microglobulin level (<3.3) and previous autologous HSCT were predictive of lower nonrelapse mortality and longer PFS and OS. Our findings indicate that allo-HSCT with RIC is associated with acceptable toxicity and durable remission and survival in relapsed or refractory MM. The use of RIC allo-HSCT earlier in the course of the disease may offer the greatest benefit.

The outcome of IgD myeloma after autologous hematopoietic stem cell transplantation is similar to other Ig subtypes.

IgD myeloma is a rare subtype of myeloma that is associated with an aggressive course, resistance to chemotherapy, and a poor outcome. We identified 17 patients with IgD myeloma, who received a hematopoietic stem cell transplantation (HCT) at our institution between August 1988 and June 2008. Fifteen of these 17 patients underwent an autologous (auto) HCT. Complete responses (CRs) were seen in 6 of 15 (40%) patients; three converted from partial response to CR, two from minimal response to CR, and one from very good partial response to CR. The overall response rate after auto HCT was 86% (13 of 15). Kaplan-Meiers estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median PFS and OS were 18 and 45 months, respectively. These results were comparable with patients receiving autologous HCT for other Ig subtypes of myeloma.

Outcome of allogeneic hematopoietic stem cell transplantation in patients with low left ventricular ejection fraction.

A high risk of regimen-related toxicity with allogeneic hematopoietic stem cell transplantation (allo-HSCT) limits this potentially curative treatment for patients with a left ventricular ejection fraction (LVEF) of > or =50%. We evaluated the frequency of cardiac complications and 100-day nonrelapse mortality (NRM) in 56 patients with a LVEF of < or =45%, who received allo HCT at our institution. The results were retrospectively compared with a matched control group with LVEF of > or =50%, which received an allogeneic stem cell transplantation (allo-SCT). After a median follow-up of 29 months in the study group, grade > or =2 cardiac complications were seen in 7 of 56 (12.5%) patients and cumulative incidence of 100-day NRM was 12.5% with no deaths from cardiac causes. In contrast, after a median follow-up of 49 months in the control group, grade >2 cardiac complications were seen in 19 of 161 patients (11.8%; P = 1.00) and cumulative incidence of 100-day NRM was 14.9% (P = .82). The presence of at least 1 of the 7 pretransplant cardiac risk factors (past history of smoking, hypertension, hyperlipidemia, coronary artery disease, arrhythmia, prior myocardial infarction, and congestive heart failure) was associated with a higher cardiac complication rate in the study group (P = .03). In conclusion, selected patients with a LVEF of < or =45% can safely receive allo-HCT without a significant increase in cardiac toxicity or NRM.

Feasibility of autologous hematopoietic stem cell transplant in patients aged ≥70 years with multiple myeloma.

Abstract We retrospectively analyzed the outcomes of all consecutive patients with myeloma (n = 84) aged ≥70 years who had received autologous hematopoietic stem cell transplant (auto HCT) between July 1999 and June 2010 at our institution. The median age at auto HCT was 72 years, the median number of prior therapies was 2.5 and the median time from diagnosis to auto HCT was 10.2 months. The conditioning regimen consisted of melphalan at 140 mg/m(2) in 10%, 180 mg/m(2) in 25% and 200 mg/m(2) in 65% of patients. The day-100 non-relapse mortality was 3%. The overall response rate at day 100 was 85% (complete response 18%, very good partial response 12%, partial response 55%). After a median follow-up of 25 months among surviving patients, the estimated progression-free survival and overall survival at 5 years were 27% and 67%, respectively. The incidence of grade II-IV toxicity, response rate and survival were similar across three melphalan dose levels. These results indicate that high-dose melphalan plus auto HCT is safe and feasible for patients with multiple myeloma aged ≥70 years and age alone should not be an exclusion criterion for auto HCT.