Explore the vast range of titles available.

Although reduced-intensity conditioning (RIC) and non-myeloablative (NMA)-conditioning regimens have been used for over a decade, their relative efficacy vs myeloablative (MA) approaches to allogeneic hematopoietic cell transplantation in patients with AML and myelodysplasia (MDS) is unknown. We compared disease status, donor, graft and recipient characteristics with outcomes of 3731 MA with 1448 RIC/NMA procedures performed at 217 centers between 1997 and 2004. The 5-year univariate probabilities and multivariate relative risk outcomes of relapse, TRM, disease-free survival (DFS) and OS are reported. Adjusted OS at 5 years was 34, 33 and 26% for MA, RIC and NMA transplants, respectively. NMA conditioning resulted in inferior DFS and OS, but there was no difference in DFS and OS between RIC and MA regimens. Late TRM negates early decreases in toxicity with RIC and NMA regimens. Our data suggest that higher regimen intensity may contribute to optimal survival in patients with AML/MDS, suggesting roles for both regimen intensity and graft vs leukemia in these diseases. Prospective studies comparing regimens are needed to confirm this finding and determine the optimal approach to patients who are eligible for either MA or RIC/NMA conditioning.

Disease relapse or progression is a major cause of death following umbilical cord blood (UCB) transplantation (UCBT) in patients with high-risk, relapsed or refractory acute lymphoblastic leukemia (ALL). Adoptive transfer of donor-derived T cells modified to express a tumor-targeted chimeric antigen receptor (CAR) may eradicate persistent disease after transplantation. Such therapy has not been available to UCBT recipients, however, due to the low numbers of available UCB T cells and the limited capacity for ex vivo expansion of cytolytic cells. We have developed a novel strategy to expand UCB T cells to clinically relevant numbers in the context of exogenous cytokines. UCB-derived T cells cultured with interleukin (IL)-12 and IL-15 generated >150-fold expansion with a unique central memory/effector phenotype. Moreover, UCB T cells were modified to both express the CD19-specific CAR, 1928z, and secrete IL-12. 1928z/IL-12 UCB T cells retained a central memory-effector phenotype and had increased antitumor efficacy in vitro. Furthermore, adoptive transfer of 1928z/IL-12 UCB T cells resulted in significantly enhanced survival of CD19 + tumor-bearing SCID-Beige mice. Clinical translation of CAR-modified UCB T cells could augment the graft-versus-leukemia effect after UCBT and thus further improve disease-free survival of transplant patients with B-cell ALL.

Allogeneic hematopoietic SCT is an effective treatment in accelerated (AP) or blast phase (BP) CML. Imatinib (IM) has transient but significant activity in advanced phases of CML, which may permit early allografting for responding patients. To identify prognostic factors in allograft recipients previously treated with IM, we analyzed 449 allogeneic hematopoietic SCTs performed from 1999 to 2004 in advanced-phase CML, using the data reported to the Center for International Blood and Marrow Transplant Research. CML patients in second chronic phase (CP2, n =184), AP ( n =185) and BP ( n =80) received HLA-identical sibling (27%), related (3%), or matched or mismatched unrelated donor (70%), peripheral blood (47%) or BM (53%) hematopoietic SCT after myeloablative (78%) or non-myeloablative (22%) conditioning. In all, 52% in CP2, 49% in AP and 46% in BP received IM before hematopoietic SCT. Disease-free survival was 35–40% for CP2, 26–27% for AP and 8–11% for BP. Cumulative incidence of acute and chronic GVHD and TRM were not affected by the stages of CML or pre-hematopoietic SCT IM exposure. Multivariate analyses showed that conventional prognostic indicators remain the strongest determinants of transplant outcomes. In conclusion, there are no new prognostic indicators of the outcomes of allogeneic hematopoietic SCT for advanced-phase CML in the IM era.

Treatment options for persons with leukemia relapsing after allogeneic transplantation are limited. We analyzed the outcome of 279 patients with acute and chronic leukemia, who relapsed after HLA-identical sibling transplantation and received a second allogeneic transplant. The influence of potential risk factors on treatment-related mortality (TRM), relapse, treatment failure (relapse or death) and overall survival after second transplantation were assessed using proportional-hazards regression. The cumulative incidences (95% confidence interval) of relapse and TRM at 5 years were 42 (36-48)% and 30 (24-36)%, respectively. The 5-year probabilities of both overall and leukemia-free survival were 28 (23-34)%. In multivariate analyses, risks of treatment failure and mortality were lower in younger patients (< or =20 years) and patients who relapsed after 6 months from first transplantation. Risks of relapse were lower in patients who relapsed after 6 months from first transplantation and in complete remission prior to second transplantation. Risks of relapse were higher after reduced-intensity conditioning regimens. Any potential advantage of using a different matched related donor for a second transplantation is not supported by these data. Although age, disease status and conditioning regimen are important, duration of remission after first transplantation appear to be the most important determinant of outcome.

Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age <60 years, induction therapy with novel agents, kidney only involvement and Auto-SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

Patients who undergo autologous peripheral blood stem cell (PBSC) transplantation experience multiple symptoms that adversely affect quality of life. We assessed symptoms during the acute phase of autologous PBSC transplantation to determine the severity of individual symptoms and to determine overall symptom profiles in 100 patients with multiple myeloma or non-Hodgkin's lymphoma. Study subjects completed the blood and marrow transplantation module of the M. D. Anderson Symptom Inventory before hospitalization, during conditioning, on day of transplantation, at nadir (the time of lowest white blood cell count) and on day 30 post-transplantation. Additional symptom, quality-of-life and medical status measures were collected. Symptom means were mild at baseline, intensified during conditioning, peaked at nadir and decreased by day 30. At nadir, the most severe symptoms for the entire patient sample were lack of appetite, fatigue, weakness, feeling sick, disturbed sleep, nausea and diarrhea. Cancer diagnosis was a significant predictor of changes in symptoms over time. The patterns of fatigue, pain, sleep disturbance and lack of appetite were significantly different for patients with multiple myeloma as compared with patients with non-Hodgkin's lymphoma.

We analyzed the clinical factors associated with late cytomegalovirus (CMV) reactivation in a group of 269 consecutive recipients of allogeneic stem cell transplant (SCT) for hematological malignancies. Eighty-four subjects (31%) experienced late CMV reactivation, including 64 with prior early reactivation and 20 with isolated late reactivation. Multivariate analyses were conducted in patients with early CMV reactivation to identify factors associated with late recurrence. Important risk factors included lymphoid diagnosis, occurrence of graft-versus-host disease (GVHD), greater number of episodes of early reactivation, persistent day 100 lymphopenia and the use of a CMV-seronegative donor graft. We combined these risk factors in a predictive model to identify those at relatively low, intermediate and high risk. The low-risk group (15% cumulative incidence, CI) encompassed patients without early CMV reactivation, and subjects transplanted for a myeloid malignancy from a matched-related (MR) donor without subsequent acute GVHD. The high-risk patients (73% CI) met all of the following criteria: (1) received an MR graft but developed GVHD, or received a non-MR graft irrespective of GVHD; (2) had more than two episodes of early reactivation; and (3) received a CMV-seronegative graft and/or remained persistently lymphopenic at day 100 after SCT. The remaining patients had an intermediate incidence of 32%.

A total of 36 consecutive patients with AML in CR underwent reduced-intensity allogeneic hematopoietic SCT (RISCT) with fludarabine and melphalan conditioning. All patients were ineligible for myeloablative transplantation because of age or comorbidity. In total, 30 patients were in first CR and six patients were in second CR. Donors were siblings in 21 (58%) patients and were unrelated in 15 (42%) patients. Hematopoietic cell transplant specific comorbidity scores ⩾3 were present in 26 (72%) patients. With a median follow-up of 52 months (range, 34–103 months), OS and PFS rates at 4 years were 71% (s.e., 8%) and 68% (s.e., 8%), respectively. At 4 years, the cumulative incidence of non-relapse mortality was 20% (s.e., 7%) and of relapse mortality was 8% (s.e., 5%). Neither OS nor PFS was affected by older age (>60 years), unrelated donor, melphalan dose, or comorbidity score. At last follow up, of the 24 surviving patients, 21 (88%) had performance status (ECOG) of 0 without any active chronic GVHD requiring steroids. Hence, RISCT with fludarabine and melphalan conditioning produces durable long-term remission in older patients with AML.

Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in blood and marrow transplant (BMT) recipients. In some subsets of these immunocompromised patients, RSV upper respiratory illnesses frequently progress to fatal viral pneumonia. The frequency of progression to pneumonia is higher during the pre-engraftment than during the post-engraftment period. Once pneumonia develops, the overall mortality is 60-80%, regardless of the treatment strategy. We performed a pilot trial of therapy of RSV upper respiratory illnesses using aerosolized ribavirin and IVIG (500 mg/kg every other day), with the goal of preventing progression to pneumonia and death. Two dosages of ribavirin were used: a conventional regimen (6 g/day at 20 mg/ml for 18 h/day) and a high-dose short-duration regimen (6 g/day at 60 mg/ml for 2 h every 8 h). Fourteen patients were treated for a mean of 13 days (range: 7-23 days). In 10 (71%) patients, the upper respiratory illness resolved. The other four (29%) patients, three of whom were in the pre-engraftment period, developed pneumonia, which was fatal in two. The most common adverse effect was psychological distress at being isolated within a scavenging tent. In conclusion, prompt therapy of RSV upper respiratory illnesses in BMT recipients with a combination of aerosolized ribavirin and IVIG was a safe and promising approach to prevent progression to pneumonia and death.

In spite of high-dose chemotherapy followed by autologous hematopoietic SCT multiple myeloma (MM) eventually recurs, highlighting the need for more effective treatment approaches. Patients received topotecan 3.5 mg/m 2 intravenously on days –6 to –2, melphalan 70 mg/m 2 intravenously on days –3 and –2 and CY 1 g/m 2 intravenously on days –6, –5 and –4. Overall response rate (ORR) consisting of complete response and partial response (CR+PR, PFS, OS and toxicity are reported. Between August 2002 to March 2004, 60 patients (34 men and 26 women) with a median age of 61 years (range 45–72) were enrolled. Forty-one patients were treated for consolidation of first remission, while 19 patients had relapsed/refractory disease. ORR was 85% (CR 12%, very good PR 43% and PR 30%). Median time to neutrophil (ANC>0.5 × 10 9 /L) and plt engraftment (>20 × 10 9 /L) was 10 (range 7–12 days) and 9 days (range 6–79 days), respectively. A majority of the common adverse events were grade 1–3 mucositis/stomatitis (65%), grade 1 or 2 nausea (59%) and grade 1 or 2 diarrhea (41%). Median PFS was 18.5 months and median OS has yet not been reached. In conclusion, topotecan, melphalan and CY is a safe and active conditioning regimen for auto hematopoietic SCT in MM. The ORR and PFS were comparable to high-dose melphalan.