Approximately 20% of patients with multiple myeloma (MM) have renal failure at diagnosis, and about 5% are dialysis-dependent. Many of these patients are considered ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) because of a high risk of treatment-related toxicity. We evaluated the outcome of 46 patient with MM and renal failure, defined as serum creatinine >2 mg/dL sustained for >1 month before the start of preparative regimen. Patients received auto-HSCT at our institution between September 1997 and September 2006. Median serum creatinine and creatinine clearance (CrCl) at auto-HSCT were 2.9 mg/dL (range: 2.0–12.5) and 33 mL/min (range: 8.7–63), respectively. Ten patients (21%) were dialysis-dependent. Median follow-up in surviving patients was 34 months (range: 5–81). Complete (CR) and partial responses (PR) after auto-HSCT were seen in 9 (22%) and 22 (53%) of the 41 evaluable patients, with an overall response rate of 75%. Two patients (4%) died within 100 days of auto-HSCT. Grade 2–4 nonhematologic adverse events were seen in 18 patients (39%) and included cardiac arrythmias, pulmonary edema, and hyperbilirubinemia. Significant improvement in renal function, defined as an increase in flomerular filtration rate (GFR) by 25% above baseline, was seen in 15 patients (32%). Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 36% and 64%, respectively. In conclusion, auto HSCT can be offered to patients with MM and renal failure with acceptable toxicity and with a significant improvement in renal function in approximately one-third of the transplanted patients. In this analysis, a melphalan (Mel) dose of 200 mg/m2 was not associated with an increase in toxicity or nonrelapse (Mel) mortality (NRM).

Cardiac tumors are a rare entity, comprised of tumors with diverse histology and natural history. We report the clinical characteristics, echocardiograhic findings, therapy and outcome of 59 patients with primary and metastatic cardiac tumors. Our institutional echocardiogram data base from 1993 through 2005 was reviewed to identify patients diagnosed with intra-cardiac tumor. A total of 59 patients with cardiac tumors were identified and included in the study. The patients' characteristics, presenting symptoms, diagnostic tests, location, histology of the tumor, treatment and the one year survival rate of this population was collected from the medical records. Of the 59 cardiac tumor cases, 16 (27%) were primary cardiac tumors and 43 (73%) were secondary cardiac tumors. The most common primary tumor was sarcoma affecting 13 (81%) of the 16 cases. Of these, 5 patients were angiosarcoma, 5 unclassified sarcoma, one myxoid sarcoma and 2 malignant fibrous histiocytoma. The mean age at presentation was 41.1 years, and the most common location was right atrium affecting 6 cases (37.5%). The most common symptom of dyspnea was present in 10 (62.5%) cases. Eleven (25.6%) of the 43 secondary cardiac tumors were metastasis from renal cell carcinoma. The mean age at presentation was 55.4 years. Right atrium was the most frequent location affecting 18 (42%) of the 43 patients. The most common presenting symptom was dyspnea in 15 (35%) cases. For both primary and secondary tumors, dyspnea was the most common symptom and right atrium was most frequently involved. Sarcoma was the most common primary cardiac tumor while metastasis from renal cell carcinoma was the most common secondary tumor.

Background High dose chemotherapy with autologous hematopoietic cell transplant (auto-HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto-HCT for relapsed patients, particularly in the era of novel therapeutics, is not well-defined. Methods We performed a retrospective analysis of all 44 myeloma patients (24 males, 20 females) who received a second auto-HCT as salvage between 1/3/1992 and 11/4/2008 at M.D. Anderson Cancer Center. Results Median interval between the first and salvage auto HCT was 30 months (range 2–78). Median age at salvage HCT was 54 years (38–73) and median number of salvage treatment regimens was 2 (range 0–5). Eleven (25%) patients had high-risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto. Ten patients (23%) experienced grade 3 or higher non-hematologic toxicity after the salvage auto-HCT. One patient died within 100 days for a treatment-related mortality of 2%. Best responses after salvage chemotherapy + salvage auto-HCT were as follows: CR+ near CR 11%, PR 79%, with an overall response rate of 90%. Eighteen (41%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 41 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) from time of salvage auto-HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression (TTP) after first auto HCT, greater number of prior therapies, African-American race, and IgG subtype were significantly associated with worse OS. Conclusions In selected myeloma patients, a second auto-HCT for salvage therapy is well tolerated with acceptable toxicity. The ORR and PFS are comparable to other salvage regimens.

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.

Haploidentical SCT (HaploSCT) has been most commonly performed using a myeloablative, TBI-based preparative regimen; however, the toxicity with this approach remains very high. We studied the feasibility of a reduced-intensity conditioning regimen in a phase II clinical trial using fludarabine, melphalan and thiotepa and antithymocyte globulin (ATG) for patients with advanced hematological malignancies undergoing T-cell depleted HaploSCT. Twenty-eight patients were entered in the study. Engraftment with donor-derived hematopoiesis was achieved in 78% of patients after a median of 13 days. Six patients experienced primary graft failure, three out of four tested patients had donor-specific anti-HLA antibodies (DSA) (P = 0.001). Toxicity included mostly infections. A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML). Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P = 0.03). HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA. Patients with overt relapse fared poorly and require novel treatment strategies.

Purpose Despite recent advances, multiple myeloma remains incurable and most patients eventually develop progressive disease. Allogeneic hematopoietic stem cell transplantation (allo HCT) offers a potentially curative option in 10–20% of patients with relapsed or refractory disease. We evaluated the outcome of patients undergoing allo HCT with reduced-intensity conditioning (RIC) for relapsed and/or refractory myeloma at our institution. Methods Fifty-one patients with heavily pretreated, relapsed myeloma, who received RIC allo HCT between 1996 and 2006, were included in this analysis. Results Median time from diagnosis to allo HCT was 34 months. Median follow-up in surviving patients was 27 months (3–98). Cumulative transplant-related mortality (TRM) at 1 year was 25%. Progression-free survival (PFS) and overall survival (OS) at 2 years were 19% and 32%, respectively. The incidence of grade II-IV acute or chronic graft-vs-host disease (GVHD) was 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 SCT. A lower β2 microglobulin (<3.3) and a prior autotransplant predicted a lower NRM, longer PFS and OS. Conclusion Allo HCT with RIC regimens is associated with acceptable toxicity and durable remission and survival in relapsed or refractory myeloma. Use of RIC allo HCT earlier in the course of the disease may offer greater benefit.

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 ≥50%. We evaluated the frequency of cardiac complications and 100-day nonrelapse mortality (NRM) in 56 patients with a LVEF of ≤45%, who received allo HCTat our institution. The results were retrospectively compared with a matched control group with LVEF of ≥50%, which received an allogeneic stem cell transplantation (allo-SCT). After a median follow-up of 29 months in the study group, grade ≥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 ≤45% can safely receive allo-HCT without a significant increase in cardiac toxicity or NRM.

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 follow-up 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.