More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc. HDIT included total body irradiation (800 cGy) with lung shielding, cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg). Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11 (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 (range, 1 to 8) years. There was a major improvement in skin (modified Rodnan skin score, ؊22.08; P < .001) and overall function (modified Health Assessment Questionnaire Disability Index, ؊1.03; P < .001) at final evaluation. Importantly, for the first time, biopsies confirmed a statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney func-

A B S T R A C T PurposeOver the past four decades, allogeneic hematopoietic cell transplantation (alloHCT) has evolved as a curative modality for patients with hematologic diseases. This study describes changes in use, technique, and survival in a population-based cohort. Patients and MethodsThe study included 38,060 patients with hematologic malignancies or disorders who underwent first alloHCT in a US or Canadian center from 1994 to 2005 and were reported to the Center for International Blood and Marrow Transplant Research. ResultsAlloHCT as treatment for acute lymphoblastic (ALL) and myeloid leukemias (AML), myelodysplastic syndrome (MDS), and Hodgkin and non-Hodgkin lymphomas increased by 45%, from 2,520 to 3,668 patients annually. From 1994 to 2005, use of both peripheral (7% to 6%) and cord blood increased (2% to 10%), whereas use of marrow decreased (90% to 27%). Despite a median age increase from 33 to 40 years and % increase in unrelated donors for alloHCT, overall survival (OS) at day 100 significantly improved for patients with AML in first complete remission after myeloablative sibling alloHCT (85% to 94%; P Ͻ .001) and unrelated alloHCT (63% to 86%; P Ͻ .001); 1-year OS improved among those undergoing unrelated alloHCT (48% to 63%; P ϭ .003) but not among those undergoing sibling alloHCT. Similar results were seen for ALL and MDS. Day-100 OS after cord blood alloHCT improved significantly from 60% to 78% (P Ͻ .001) for AML, ALL, MDS, and chronic myeloid leukemia. Use of reduced-intensity regimens increased, yielding OS rates similar to those of myeloablative regimens. ConclusionSurvival for those undergoing alloHCT has significantly improved over time. However, new approaches are needed to further improve 1-year OS.

Success of hematopoietic-cell transplantation (HCT) can vary by race, but the impact of socioeconomic-status (SES) is not known. To evaluate the role of race and SES, we studied 6207 unrelated-donor myeloablative HCT recipients transplanted between 1995–2004 for acute or chronic leukemia or myelodysplastic syndrome. Patients were reported by transplant center to be White (n=5253), African-American (n=368), Asian/Pacific-Islander (n=141), or Hispanic (n=445). Patient income was estimated from residential ZIP Code at time of HCT. Cox-regression analysis adjusting for other significant factors showed that African-American (but not Asian or Hispanic) recipients had worse overall survival (OS) (relative-risk [RR] 1.47 (95% CI 1.29–1.68), P<0.001) compared to Whites. Treatment-related mortality (TRM) was higher in African-Americans (RR 1.56, (1.34–1.83), P<0.001) and in Hispanics (RR 1.30, (1.11–1.51), P=0.001). Across all racial groups, patients with median incomes in the lowest quartile (<$34,700) had worse OS (RR 1.15 (1.04–1.26), P=0.005) and higher risks of TRM (RR 1.21 (1.07–1.36), P=0.002). Inferior outcomes among African-Americans are not fully explained by transplant-related factors or SES. Potential other mechanisms such as genetic polymorphisms that impact drug metabolism or unmeasured co-morbidities, socioeconomic factors and health behaviors may be important. Low SES, regardless of race, has a negative impact on unrelated donor HCT outcomes.

Reduced-intensity conditioning (RIC) regimens have been increasingly used for allogeneic hematopoietic stem cell transplantation (HSCT) in follicular lymphoma (FL). We compared traditional myeloablative conditioning regimens to RIC in FL. Outcomes of HLA-identical sibling HSCT for FL in 208 recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1997 and 2002 were studied. Conditioning regimens were categorized as myeloablative (N = 120) or RIC (N = 88). Use of RIC regimens increased from <10% of transplants in 1997 to >80% in 2002 signaling a major shift in practice. Patients receiving RIC were older and had a longer interval from diagnosis to transplant. These differences did not correlate with outcomes. Median follow-up of survivors was 50 months (4-96 months) after myeloablative conditioning versus 35 months (4-82 months) after RIC (P < .001). At 3 years, overall survival (OS) for the myeloablative and RIC cohorts were 71 (63%-79%) and 62 (51%-72%; P = .15) and progression free survival (PFS), 67 (58%-75%) and 55 (44%-65%; P = .07), respectively. Lower Karnofsky performance score (KPS) and resistance to chemotherapy were associated with higher treatment-related mortality (TRM) and lower OS and PFS. On multivariate analysis, an increased risk of lymphoma progression after RIC was observed (relative risk = 2.97, P = .04). RIC has become the de facto standard in allogeneic HSCT for FL, and appears to result in similar long-term outcomes. Although disease-free survival (DPS) is similar compared to myeloablative conditioning, an increased risk of late disease progression after RIC is concerning.

The American Society for Transplantation and Cellular Therapy (ASTCT) published its first white paper on indications for autologous and allogeneic hematopoietic cell transplantation (HCT) in 2015. It was identified at the time that periodic updates of indications would be required to stay abreast with state of the art and emerging indications and therapy. In recent years the field has not only seen an improvement in transplantation technology, thus widening the therapeutic scope of HCT, but additionally a whole new treatment strategy using modified immune effector cells, including chimeric antigen receptor T cells and engineered T-cell receptors, has emerged. The guidelines review committee of the ASTCT deemed it optimal to update the ASTCT recommendations for indications for HCT to include new data and to incorporate indications for immune effector cell therapy (IECT) where appropriate. The guidelines committee established a multiple stakeholder task force consisting of transplant experts, payer representatives, and a patient advocate to provide guidance on indications for HCT and IECT. This article presents the updated recommendations from the ASTCT on indications for HCT and IECT. Indications for HCT/IECT were categorized as (1) Standard of care, where indication is well defined and supported by evidence; (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but have been shown to be effective therapy; (3) Standard of care, rare indication, for rare diseases where demonstrated effectiveness exists but large clinical trials and observational studies are not feasible; (4) Developmental, for diseases where preclinical and/or early-phase clinical studies show HCT/IECT to be a promising treatment option; and (5) Not generally recommended, where available evidence does not support the routine use of HCT/IECT. The ASTCT will continue to periodically review these guidelines and update them as new evidence becomes available.