International recommendations for screening and preventative practices for long-term survivors of transplantation and cellular therapy: a 2023 update.

As hematopoietic cell transplantation (HCT) and cellular therapy expand to new indications and international access improves, the volume of HCT 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 pre-, peri- and post-transplant exposures and other underlying risk-factors. Guidelines for screening and preventive practices for HCT survivors were originally published in 2006 and updated in 2012. To review contemporary literature and update the recommendations while considering the changing practice of HCT and cellular therapy, an international group of experts was again convened. 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 special needs of patients with distinct underlying HCT indications or comorbidities (e.g., 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.

International Recommendations for Screening and Preventative Practices for Long-Term Survivors of Transplantation and Cellular Therapy: A 2023 Update.

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.

Cell Therapy Informatics: Updates on the Integration of HCT/IEC Functionalities into an Electronic Medical Record System in the US to Promote Efficiency, Patient Safety, Research, and Data Interoperability.

The use of electronic health/medical record (EMR) systems has streamlined medical practice and improved efficiency of clinical care in recent years. However, EMR systems are not generally well designed to support research and tracking of longitudinal outcomes across populations, which are particularly important in hematopoietic stem cell transplantation (HCT) and immune effector cell therapy (IEC), where data reporting to registries and regulatory agencies are often required. Since its formation in 2014, the HCT EMR user group has worked with a large EMR vendor (Epic) to develop many functionalities within the EMR to improve the care of HCT/IEC patients and facilitate the capture of HCT/IEC data in an easily interoperable format. Awareness and the widespread adoption of these new tools among transplant centers remains a challenge, however. In this report, we aim to increase awareness and adoption of these new features in the Epic EMR across the transplantation community, advocate for the use of data standards, and promote future collaboration with other commercial EMRs to develop standardized HCT/IEC content to improve patient care and facilitate interoperable data exchange.

Impact of Public Reporting of Center-Specific Survival Analysis Scores on Patient Volumes at Hematopoietic Cell Transplant Centers.

The Center for International Blood and Marrow Transplant Research reports the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) at United States transplantation centers (TC) annually through its Center-Specific Survival Analysis (CSA). The CSA compares the actual 1-year overall survival (OS) and predicted 1-year OS rate after alloHCT at each TC, which is then reported as 0 (OS as expected), -1 (OS worse than expected), or 1 (OS better than expected). We evaluated the impact of public reporting of TC performance on their alloHCT patient volumes. Ninety-one TCs that serve adult or combined adult and pediatric populations and had CSA scores reported for 2012-2018 were included. We analyzed prior-calendar-year TC volume, prior-calendar-year CSA score, whether the CSA score had changed in the prior year from two years earlier, calendar year, TC type (adult only vs. combined adult and pediatric), and years of alloHCT experience for their impact on patient volumes. A CSA score of -1, as compared with 0 or 1, was associated with an 8% to 9% reduction in the mean TC volume (P < 0.001) in the subsequent year, adjusting for the prior year center volume. Additionally, being a TC neighboring an index TC with a -1 CSA score, was associated with a 3.5% increase in mean TC volume (P = 0.04). Our data show that public reporting of CSA scores is associated with changes in alloHCT volumes at TCs. Additional investigation into the causes of this shift in patient volume and the impact on outcomes is ongoing.

Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research.

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.

Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the national marrow donor program.

To determine the long-term outcome of patients undergoing unrelated donor transplantation (URD) after a reduced intensity conditioning (RIC) regimen, we performed a retrospective analysis of the transplant outcomes of the first 5 years of RIC experience as reported to the National Marrow Donor Program (NMDP). Patients were included if they were older than 18 years and had undergone a URD transplant procured through the NMDP from January 1, 1996 until May 31, 2001, with an RIC regimen for a hematologic malignancy. The number of URDs performed using an RIC increased from 59 during 1996 to 1999, to 149 in the year 2000. RIC recipients were older (53 vs. 33 years) and had a higher likelihood of having advanced disease (81% vs. 51%) when compared to patients undergoing a myeloablative conditioning regimen during the same time period. The 5-year survival rate is 23% (95% confidence interval [CI]; 18, 28), whereas the 5 year incidence of progression/relapse is 43.4% (95% CI; 37,49). Prognostic factors for better overall survival on multivariate analysis were earlier disease stage, longer time to transplant from diagnosis, better HLA match, >or=90% performance score, and use of peripheral blood stem cells. This analysis demonstrates that long-term survival and disease control can be obtained with URD progenitor cell transplantation after RIC conditioning. However, only prospective trials will define the optimal role of this therapy in patients with hematologic malignancies. Therefore, URD transplantation with RIC should continue to be explored in the context of clinical trials.

Autologous transplantation for diffuse aggressive non-Hodgkin lymphoma in first relapse or second remission.

We evaluated the results of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with diffuse aggressive non-Hodgkin lymphoma (NHL) in first relapse (Rel 1) or second complete remission (CR 2). Data were evaluated from the Autologous Blood and Marrow Transplant Registry on 429 patients with diffuse aggressive NHL who underwent transplantation in Rel 1 or CR 2. Transplantations were performed between 1989 and 1996 and were reported to the Autologous Blood and Marrow Transplant Registry by 93 centers in North and South America. The probability of 3-year survival was 44% (95% confidence interval [CI], 33%-55%). The probability at 3 years of progression-free survival was 31% (95% CI, 27%-36%). Patients who underwent transplantation in CR 2 had a 3-year probability of progression-free survival of 38% (95% CI, 30%-46%) compared with 28% (95% CI, 22%-33%) for those who were not in remission at the time of transplantation (P <.001). In multivariate analysis, chemotherapy resistance, increased lactic dehydrogenase at diagnosis, an interval of <12 months from diagnosis to relapse, age >or=40 years, and use of myeloid growth factors to accelerate posttransplantation bone marrow recovery were adverse predictors of survival. High-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with diffuse aggressive NHL in CR 2 or Rel 1 resulted in better outcome for patients with chemotherapy-sensitive disease, longer relapse-free intervals, and age <40 years. Exposure to myeloid growth factors to accelerate recovery for recipients of bone marrow grafts may increase the risk of disease progression or death.