Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies.

As the threshold nucleated cell dose for one-unit umbilical cord blood (UCB) in adults has not to date been firmly established, we prospectively compared one- vs two-unit UCB transplantation after reduced intensity conditioning (RIC) in adult patients with hematological malignancies. Study design specified one-UCB unit if the cryopreserved total nucleated cell (TNC) dose was 2.5 × 10(7)/kg recipient weight, otherwise two units matched at minima of 4/6 HLA loci to the patient and 3/6 to each other were infused. A total of 27 patients received one unit; 23 patients received two units. Median time to ANC >500/µL was 24 days (95% confidence interval 22-28 days), 25 days for one unit and 23 days for two units (P=0.99). At day 100, ANC >500/µL was 88.4 and 91.3% in the one- and two-unit groups (P=0.99), respectively. Three-year EFS was 28.6% and 39.1% in the one- and two-unit groups (P=0.71), respectively. Infusion of two units was associated with a significantly lower relapse risk, 30.4% vs 59.3% (P=0.045). Infused cell doses (TNC, CD3(+), CD34(+) and CD56(+)CD3(neg)) did not impact on engraftment, OS or EFS. Taken together, one-unit UCB transplantation with a threshold cell dose 2.5 × 10(7)/kg recipient weight after RIC is a viable option for adults, although infusion of two units confers a lower relapse incidence.

The evolution of hematopoietic SCT in myelodysplastic syndrome.

Allogeneic hematopoietic SCT (allo-HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Numerous myeloablative (MA), nonmyeloablative SCT (NST) and reduced conditioning transplant (RIC) studies have included MDS patients. Twenty-four MA HCT studies published from 2000 and 2008 reported OS and disease-free survival (DFS) ranging from 25 and 16% at 2 years to 52 and 50% at 4 years. In these publications, the incidence of grades II-IV acute GVHD was 18-100%, chronic GVHD 13-88%, relapse risk 24% at 1 year to 54.5% at 4 years and TRM 19% at day 100 to 61% at 5 years. From 2003 to 2008, 30 publications combining RIC and NST reported OS and DFS from 22 and 20% at 2 years to 79 and 79% at 4 years. Incidence of grades II-IV acute GVHD ranged from 9 to 63%, chronic GVHD 18 to 80%, relapse risk 6 to 61% and TRM 0% at day 100 to 34% at 5 years. The wide range in the published results leaves many unanswered questions. Although no ideal transplant conditioning has emerged, many of the MA and RIC studies used BU-based regimens and used a recipient age cutoff of 50-55 years for MA HCT. Similarly, there is no agreement on the use of induction or hypomethylating therapy before HCT, but azacitidine and decitabine are gaining increasing attention as a bridge to HCT. Until recently, the International Prognostic Scoring System (IPSS) dictated the use and timing of HCT. The WHO classification and WHO Prognostic Scoring System (WPSS) may be better suited in predicting the outcomes and should probably be incorporated in transplant algorithms. Most published MDS transplant series combine matched related donors (MRD) and matched unrelated donors (MUD). Umbilical cord blood (UCB) grafts will likely broaden the population of MDS patients eligible for allografting, but outcome data for MDS are scant. At this time, it is reasonable to consider the availability of an MRD or MUD as separate from an UCB graft in the decision of transplantation for MDS. The development of RIC, improvements in supportive therapy and alternative donor selection will provide better OS for MDS patients undergoing transplantation. Simultaneously, better understanding and medical therapy of MDS are leading us to re-examine patient selection and the timing of HCT. The results of HCT for MDS continue to improve together with the outlook of patients afflicted with myelodysplasia.