Outcome of Patients with Immunoglobulin Light-Chain Amyloidosis with Lung, Liver, Gastrointestinal, Neurologic, and Soft Tissue Involvement after Autologous Hematopoietic Stem Cell Transplantation.

There is limited information on the outcome when organs other than heart or kidneys are involved by immunoglobulin light-chain amyloidosis (AL). We report the outcome of 53 patients with AL with gastrointestinal (GI), peripheral nerve (PN), liver, lung, or soft-tissue involvement, who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution between 1997 and 2013. The median age at auto-HCT was 56 years (range, 35 to 74). One, 2, 3, or 4 organs were involved in 43%, 22%, 28%, and 4% of patients, respectively. Concurrent cardiac, renal, or both were involved in 24 (45%) patients. Forty-six patients received induction therapy before auto-HCT. The 100-day and 1-year treatment-related mortality (TRM) were 3.8% (n = 2) and 7.5% (n = 4), respectively. Forty-one (80%) patients achieved a hematologic response. Organ response at 1 year after auto-HCT was seen in 23 (57%) of the 40 evaluable patients. With a median follow-up of 24 months, the median progression-free survival and overall survival (OS) were 36 and 73 months, respectively. Auto-HCT was associated with a low TRM, durable organ responses, and a median OS of > 6 years in selected patients with AL and GI, PN, liver, lung, or soft-tissue involvement.

A randomized phase II trial of fludarabine/melphalan 100 versus fludarabine/melphalan 140 followed by allogeneic hematopoietic stem cell transplantation for patients with multiple myeloma.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment for multiple myeloma (MM); however, because of high treatment-related mortality (TRM), its role is not well defined. Patients with newly diagnosed, relapsed, or primary refractory myeloma were enrolled in a randomized phase II trial of 2 reduced-intensity conditioning regimens: fludarabine 120 mg/m(2) + melphalan 100 mg/m(2) (FM100) versus fludarabine 120 mg/m(2) + melphalan 140 mg/m(2) (FM140) before allo-HCT from related or unrelated donors. Fifty patients underwent allo-HCT using FM100 (n = 23) or FM140 (n = 27) conditioning between April 2002 and 2011. There were no significant differences between FM100 and FM140 in time to neutrophil engraftment (P = .21), acute grade II to IV graft-versus-host disease (GVHD) (P = 1.0), chronic GVHD (P = .24), response rate (P = 1.0), TRM (13% versus 15%, P = 1.0), median progression-free survival (PFS), 11.7 versus 8.4 months, P = .12, and median overall survival (OS), 35.1 versus 19.7 months, P = .38. Cumulative incidence of disease progression in FM100 and FM140 was 43% and 70%, respectively (P = .08). Recurrent disease was the most common cause of death for both FM100 (26%) and FM140 (44%), P = .24. On multivariate analysis, disease status at allo-HCT, complete response or very good partial response (VGPR) was significantly associated with longer PFS (15.6 versus 9.6 months in patients with

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.

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.