Douglas Rizzo

During the 2006 BMT Tandem Meetings, a workshop was convened by the Center for International Blood and Marrow Transplant Research (CIBMTR) to discuss conditioning regimen intensity and define boundaries of reduced-intensity conditioning (RIC) before hematopoietic cell transplantation (HCT). The goal of the workshop was to determine the acceptance of available RIC definitions in the transplant community. Participants were surveyed regarding their opinions on specific statements on conditioning regimen intensity. Questions covered the "Champlin criteria," as well as operational definitions used in registry studies, exemplified in clinical vignettes. A total of 56 participants, including transplantation physicians, transplant center directors, and transplantation nurses, with a median of 12 years of experience in HCT, answered the survey. Of these, 67% agreed that a RIC regimen should cause reversible myelosuppression when administered without stem cell support, result in low nonhematologic toxicity, and, after transplantation, result in mixed donor-recipient chimerism at the time of first assessment in most patients. Likewise, the majority (71%) agreed or strongly agreed that regimens including < 500 cGy of total body irradiation as a single fraction or 800 cGy in fractionated doses, busulfan dose < 9 mg/kg, melphalan dose <140 mg/m(2), or thiotepa dose < 10 mg/kg should be considered RIC regimens. However, only 32% agreed or strongly agreed that the combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) should be considered a RIC regimen. These results demonstrate that although HCT professionals have not reached a consensus on what constitutes a RIC regimen, most accept currently used criteria and operational definitions. These results support the continued use of current criteria for RIC regimens until a consensus statement can be developed.

Multivariate analysis was performed to determine the independent factors affecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chronic GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-depleted (TCD) marrow allografts who received transplants at a single center between 1991 and 2000. All patients received grafts partially depleted of CD3+ T cells by complement-mediated lysis using 2 narrow-specificity monoclonal antibodies (MoAbs), T10B9.1A-31 (n = 400) or Muromonab-Orthoclone OKT3 (n = 81). Factors considered in the analysis included patient/donor sex, age, cytomegalovirus (CMV) status, and ABO blood group along with T-cell dose, disease, and disease status, donor relationship, HLA antigen (Ag)mismatch (MM), growth-factor use, anti-thymocyte globulin use, year of transplantation, and the MoAb used for TCD. The results showed an association of HLA with an increased relative risk (RR) of aGVHD for recipients of grafts from relateddonors that were > or =2 Ag MM (n = 73, RR = 2.09, P = .005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), and > or =2 Ag MM UR donors (n = 34, RR = 2.68, P = .003) compared with the baseline matched-sibling group (n = 121). No increased risk of aGVHD was seen for 0 to 1 Ag MM family donors (n = 24) or 1 Ag MM UR donors (n = 99). aGVHD risk was increased with minor, but not major or major-minor, ABO disparity (RR = 2.0, P = .003) compared with that of ABO-identical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, the use of OKT3 and not the T-cell dose was associated with increased aGVH-D risk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associated with patient age of >20 years (RR = 2.2, P < .0001) and with CMV status (positive patient/negative donor, RR = 1.9, P = .002). Decreased survival was associated with older age (>20 years), a > or =2 Ag MM related donor, a 1 or > or =2 Ag MM UR donor, risk group, and a CMV-positive patient/-negative donor pair. There was no difference in survival for 0 to 1 Ag MM related or matched UR donors compared with the baseline group. These data indicate that there are quantitative as well as potential qualitative differences in outcome depending on the TCD method. Expected and unexpected risk factors for GVHD and survival were associated with partial TCD. Our data support the consideration of ABO match in donor selection, the preferential selection of CMV-positive donors for CMV-positive recipients, and the acceptance of 1 but not > or =2 Ag HLA MM donors.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the number of HCTs performed annually continues to rise. Parallel improvements in HCT techniques and supportive care entails more patients surviving long term, creating further emphasis on survivorship needs. Survivors are at risk for developing late complications secondary to pretransplantation, peritransplantation, and post-transplantation exposures and other underlying risk factors. Guidelines for screening and preventive practices for HCT survivors were originally published in 2006 and then updated in 2012. An international group of experts was convened to review the contemporary literature and update the recommendations while considering the changing practices of HCT and cellular therapy. This review provides updated pediatric and adult survivorship guidelines for HCT and cellular therapy. The contributory role of chronic graft-versus-host disease (cGVHD) to the development of late effects is discussed, but cGVHD management is not covered in detail. These guidelines emphasize the special needs of patients with distinct underlying HCT indications or comorbidities (eg, hemoglobinopathies, older adults) but do not replace more detailed group-, disease-, or condition-specific guidelines. Although these recommendations should be applicable to the vast majority of HCT recipients, resource constraints may limit their implementation in some settings.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term costsavings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.