Serious acute or chronic graft-versus-host disease after hematopoietic cell transplantation: a comparison of myeloablative and nonmyeloablative conditioning regimens

We previously reported a 25% incidence of serious graft-versus-host disease (GVHD) (that is, acute or chronic GVHD that caused death, lengthy hospitalization or disability, or resulted in recurrent major infections) among 171 hematopoietic cell transplantation (HCT) recipients after nonmyeloablative (NMA) regimen. Here we present a retrospective study applying the same criteria to 264 recipients of peripheral blood HCT after myeloablative (MA) regimen, and compare the results with the previous study after additional follow-up. The MA group was younger and had lower comorbidity scores at HCT than those in the NMA group. The overall incidence of serious GVHD was 17% (44/264) in the MA group versus 28% (48/171) in the NMA group. The adjusted hazard ratio (HR) of serious GVHD in the MA group compared to the NMA group was 0.65 (95% CI, 0.4-1.1); P = 0.13, and if follow-up was censored at the onset of recurrent or progressive malignancy, HR was 0.67 (95% CI, 0.4-1.3), P = 0.22. We conclude that the choice between MA and NMA regimens does not greatly affect the risk of serious GVHD as an overall indicator of outcomes related to either acute or chronic GVHD. Serious GVHD maybe considered as an endpoint in clinical trials with GVHD-related outcomes.411088789

Potential Prognostic Biomarkers for Bone Metastasis from Hepatocellular Carcinoma

Whether or not variations in gene and protein expression in hepatocellular carcinoma present at the time of surgery can enable the identification of patients at high risk for developing bone metastasis was examined

European experience and risk factor analysis of donor cell-derived leukaemias/MDS following haematopoietic cell transplantation.

Donor cell leukaemia (DCL) is a rare complication of allogeneic haematopoietic cell transplantation (HCT). We have investigated the prevalence and outcome of donor cell haematology malignancies within centres registered with the European Society of Blood and Marrow transplantation (EBMT). We have sought to identify risk factors to shed light on the pathogenesis of DCL as a model for leukaemogenesis. DCL cases were identified by questionnaire and a follow-up questionnaire requested detailed data. Control subjects from the EBMT registry who had not developed DCL were used for a matched pair analysis to identify risk factors. We identified 38 patients with DCL; the estimated prevalence was 80.5/100,000 transplants. Patients were predominantly treated for haematological malignancy. A clone was retrospectively identified in 7/25 (28%) donors for whom data was available. Overall survival was poor with 29/38 patients dead a median of 11 (range 0-91) months after DCL diagnosis. Matched case-pair analysis identified three factors on multivariate analysis as significantly associated with an increased risk for DCL: use of growth factors within the first 100 days after transplantation, in vivo T-cell depletion and multiple allografts. The risk factors identified, support reduced immune surveillance and replicative stress as pathogenic in the development of DCL

Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning

Allogeneic hematopoietic cell transplantation ( HCT) following nonmyeloablative conditioning has been extensively evaluated in patients with hematologic malignancies who are ineligible for conventional HCT because of age or medical comorbidities. Nonmyeloablative regimens have led to an initial state of mixed hematopoietic chimerism defined as coexistence of donor- and host-derived hematopoiesis. While nonmyeloablative regimens have been associated with reduced regimen-related toxicities in comparison with conventional myeloablative conditioning, graft rejection, graft-versus-host disease ( GVHD), and disease progression have remained significant challenges. In this article, after briefly introducing current techniques for chimerism assessment, we describe factors affecting donor chimerism levels after nonmyeloablative conditioning, and then review data suggesting that chimerism assessment early after HCT might help identify patients at risk for graft rejection, GVHD and relapse/progression. Finally, we discuss how these observations have opened the way to further research protocols evaluating manipulation of postgrafting immunosuppression, and/or infusion of donor immune cells