Allogeneic Stem Cell Transplantation for Relapsed or Refractory Lymphoma after Conditioning with BEAM/Fludarabine/TBI

AbstractAllogeneic stem cell transplant (SCT) after high-dose conditioning with BEAM/fludarabine/total body irradiation (TBI) in patients with relapsed or refractory lymphoma has shown promising results in a pilot study. In this trial, we treated 50 consecutive patients with refractory or relapsed lymphoma or chronic lymphocytic leukemia (CLL). The patients included were considered to have poor-prognosis disease (eg, one-third was chemo-refractory at transplantation and more than one-half had failed previous autologous or allogeneic SCT). All patients engrafted and achieved full donor chimerism. Grade II-IV acute graft-versus-host disease (aGVHD) occurred in 64% of patients (95% confidence interval [CI], 52% to 79%), and chronic GVHD (cGVHD) in 51% (95% CI, 36% to 66%). At 3 years, overall survival was 61% (95% CI, 46% to 75%). Progression-free survival was 55% (95% CI, 40% to 70%), with 30% (95% CI, 19% to 47%) transplantation-related mortality and a relapse incidence of 15% (95% CI, 7% to 32%). Disease classification and stage as well as remission status at transplantation and type of previous treatment (including previous SCT) had no significant impact on transplantation outcome. In conclusion, allogeneic SCT after BEAM/fludarabine/TBI provides excellent tumor control with complete and durable remissions in patients with poor-prognosis lymphoma and CLL. High rates of GVHD and GVHD-related mortality associated with this regimen are a major concern and warrant modification of the regimen in the future

High-Dose Melphalan Re-Induction with or without Stem Cell Support Prior to Myeloablative Allogeneic Stem Cell Transplantation in Patients with Advanced Relapsed or Refractory Acute Myeloid Leukemia.

Abstract Abstract 2271 Poster Board II-248 Relapsed/refractory acute myeloid leukemia (AML) has a poor prognosis and the therapeutic options are limited. Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) may be used, however its outcome is poor compared to patients treated in remission. Recently, high-dose melphalan (HDM) with autologous stem cell support has shown promising activity in patients with relapsed AML. Few data exist on the impact of HDM re-induction in AML patients planned for allo-HSCT. We analyzed the outcome of 23 patients with highly advanced relapsed and/or refractory AML re-induced with HDM followed by myeloablative allo-HSCT. The re-induction regimen consisted of a single dose of melphalan 200mg/m2 i.v. on day -1. Where possible, stem cell support was given (group 1; n=12): patients for whom a previously harvested autologous hematopoietic stem cell product was available received autologous HSCT on day 0 (n=3). Patients with an HLA-identical sibling donor were allocated to tandem allo-HSCT and received a first CD34-selected graft from their sibling donor (n=8). One patient relapsing after haploidentical HSCT and scheduled for unrelated HSCT was provided with stem cell support from his previous haploidentical donor. All other patients, planned for allo-HSCT from a matched unrelated, mismatched related or cord blood donor had HDM without stem cell support (group 2; n=11). Both groups were prospectively scheduled to undergo a second conditioning regimen 2-4 weeks after HDM consisting of cyclophosphamide/busulfan or cyclophosphamide/12 Gy total body irradiation +/- etoposide followed by allo-HSCT. The primary endpoints were blast clearance and the number of patients proceeding to allo-HSCT. Secondary endpoints were the toxicity and feasibility of HDM and final outcome. From March 2005 to April 2009, 12 males and 11 females aged 21 to 69 years (median 39) with advanced AML were included. Seven were in primary induction failure, 7 in untreated relapse, 4 were refractory to salvage chemotherapy and 5 were in second relapse after successful salvaging. Nine patients relapsed after a previous HSCT, seven after allo, two after autologous HSCT. Eighteen patients (78%) achieved complete remission, defined as absence of blasts in the bone marrow, peripheral blood or extramedullary sites. The four remaining patients had substantial reduction of the initial leukemia burden warranting treatment continuation. None of the patients died within 25 days of HDM. Twenty patients (87%) went on to the second phase of the planned protocol, to full conditioning and allo-HSCT (9 HLA-identical sibling, 2 haploidentical donor, 9 unrelated donor). Three patients went off continuation, 1 due to progressive disease, 2 due to severe toxicity (1 combined cytomegalovirus and respiratory syncytial virus pneumonitis; 1 obstructive lung disease). There was no difference between patients with (group 1) or without (group 2) stem cell support after HDM regarding mucositis grade 3 and 4 (63% versus 54%; p=0.66), other organ toxicity or overall survival (OS) after the second HSCT (76 versus 87 days, median; p= 0.74). Of the patients proceeding to allogeneic HSCT, 2 (10%) were alive and in remission at last follow-up (Figure). Seven patients (35%) had died from TRM (infection n=2, bleeding n=2, veno-occlusive disease n=2, interstitial pneumonitis n=1) at a median of 32 days after allo-HSCT. Eleven patients (55%) relapsed at a median of 84 days (range 42-1019) after allo-HSCT. Median progression free survival (PFS) was 74 days and median OS 79 days after HSCT. Both patients alive and well had had a 1st CR of more than one year's duration. In conclusion, our study demonstrates that HDM is effective in achieving complete blast elimination in patients with highly advanced relapsed/refractory AML. However – compared to historical controls of patients directly transplanted for relapsed/refractory AML – leukemia burden reduction with HDM did not translate into improved overall survival after HSCT. Figure Figure. Disclosures: Off Label Use: This presentation includes results of the off-label use of melphalan as a re-induction regimen for AML. Gratwohl:Amgen: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Advisory Board, Research Funding; Roche: Research Funding; Pfizer: Research Funding. </jats:sec

Patient preferences for allogeneic haematopoietic stem cell transplantation: how much benefit is worthwhile from the patient’s perspective?

AbstractOncological studies have shown that patients consider small benefits sufficient to make adjuvant chemotherapy worthwhile. We sought to determine the minimal survival benefits that patients considered enough to legitimate allogeneic haematopoietic stem cell transplantation (HCT) and the factors associated with patient preferences. One hundred eighty-four patients having previously received allogeneic HCT at our centre were included and completed a questionnaire exploring patient expectations elicited by time trade-off scenarios as well as quality of life (QoL), symptoms of graft-versus host disease (GvHD) and sociodemographic characteristics. The majority of patients considered a minimal survival benefit of at least 5 (38.6%) or 10 years (41.9%) sufficient to justify HCT, with less than 5% considering survival &lt; 1 year sufficient to warrant HCT. In terms of minimal cure rate, a cumulative 14.8% of patients accepted cure rates below 30% and 30.6% rates below 50%. Likelihood-ratio tests were significant for the effect of age at transplant on expected minimal survival (p = 0.007) and cure rates (p = 0.0001); that is, younger patients at HCT were more likely to accept smaller survival and cure rates. Pre-transplant risk score, QoL, GvHD score and sociological factors did not seem to influence patients’ expectations. In conclusion, patient expectations of treatment were much higher than what had been reported in oncological studies. Patients who experienced HCT considered a survival superior to 1 year and cure rates above 50% sufficient to make it worthwhile. Younger patients were more likely to accept smaller benefits; no other predictors for preferences could be detected.</jats:p

Forty years of haematopoietic stem cell transplantation: a review of the Basel experience

The purpose of this study was to examine changes in haematopoietic stem cell transplant (HSCT) characteristics and outcome in our combined paediatric and adult programme over the past four decades, since its implementation in 1973. The total number of transplant procedures rose from 109 in the first decade (1973-82) to 939 in the last decade (2003-12). Transplant characteristics changed significantly over time: patient age increased, peripheral blood largely replaced bone marrow as stem cell source, unrelated donors became an alternative to matched siblings, and patients are increasingly transplanted in more advanced disease stages. Advances such as improved supportive care and histocompatibility typing resulted in a steady decrease of transplant-related mortality after allogeneic HSCT (43% in the first decade, 22% in the last decade). Despite this, unadjusted survival rates were stable in the last three decades for allogeneic HSCT (approximately 50% 5-year survival) and in the last two decades for autologous HSCT (approximately 60% 5-year survival). After adjustment for covariates such as donor type, age and stage, the relative risk of treatment failure continuously dropped (for allogeneic HSCT: first decade 1.0, second decade 0.58, third decade 0.51, last decade 0.41). Collectively, these data suggest that improvements in peri- and post-transplant care have allowed considerable extension of transplant indications without having a negative impact on outcome

Racial/Ethnic Minority Youth With Recent-Onset Type 1 Diabetes Have Poor Prognostic Factors

OBJECTIVE To compare races/ethnicities for characteristics, at type 1 diabetes diagnosis and during the first 3 years postdiagnosis, known to influence long-term health outcomes. RESEARCH DESIGN AND METHODS We analyzed 927 Pediatric Diabetes Consortium (PDC) participants &amp;lt;19 years old (631 non-Hispanic white [NHW], 216 Hispanic, and 80 African American [AA]) diagnosed with type 1 diabetes and followed for a median of 3.0 years (interquartile range 2.2–3.6). Demographic and clinical data were collected from medical records and patient/parent interviews. Partial remission period or “honeymoon” was defined as insulin dose–adjusted hemoglobin A1c (IDAA1c) ≤9.0%. We used logistic, linear, and multinomial regression models, as well as repeated-measures logistic and linear regression models. Models were adjusted for known confounders. RESULTS AA subjects, compared with NHW, at diagnosis, were in a higher age- and sex-adjusted BMI percentile (BMI%), had more advanced pubertal development, and had higher frequency of presentation in diabetic ketoacidosis, largely explained by socioeconomic factors. During the first 3 years, AA subjects were more likely to have hypertension and severe hypoglycemia events; had trajectories with higher hemoglobin A1c, BMI%, insulin doses, and IDAA1c; and were less likely to enter the partial remission period. Hispanics, compared with NHWs, had higher BMI% at diagnosis and over the three subsequent years. During the 3 years postdiagnosis, Hispanics had higher prevalence of dyslipidemia and maintained trajectories of higher insulin doses and IDAA1c. CONCLUSIONS Youth of minority race/ethnicity have increased markers of poor prognosis of type 1 diabetes at diagnosis and 3 years postdiagnosis, possibly contributing to higher risk of long-term diabetes complications compared with NHWs. </jats:sec