Delayed platelet recovery after allogeneic transplantation: a predictor of increased treatment-related mortality and poorer survival

We conducted a single-arm prospective study in 50 patients who received the combination of an haploidentical stem cell graft and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. The median time for neutrophil engraftment was 13 days (11-20 days), and for platelets was 15 days (11-180 days). All surviving patients attained complete haploidentical engraftment except three patients who presented a mixed engraftment with increasing cord blood and decreasing haplo mismatch chimerism during the first 4 months after transplantation. The cumulative incidence of grade II-IV acute GVHD was 20% ± 0.327% at day þ 100, and the incidence of chronic GVHD was 19.26% ± 1.0% at 1 year. The 1-year cumulative incidence of relapse was 19.78%±1%, and the TRM was 16.2%±0.54%. At 1 year, overall survival was 78.6%±7.6% and PFS 64.0%±11.0%. The BU/CY-based conditional regimen showed a significant superiority over TBI/CY on PFS (relative risk ¼ 5.012, 95% confidence interval, 1.146-21.927, P ¼ 0.032). In conclusion, the co-infusion of an unrelated cord blood unit may potentially improve the outcome of haploidentical allogeneic hematopoietic SCT.

Section: Discussionmentioning

confidence: 99%

Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study

Chen

et al. 2013

“…To our knowledge, post transplant monocyte levels have not previously been associated with acute GVHD, although pretransplant recipient monocyte counts have previously been reported to increase this risk. 24 Poor platelet recovery is similarly associated with increased nonrelapse mortality due to acute GVHD, 25 and whether any impact of ALC and AMC recovery on acute GVHD is also associated with or independent of platelet recovery will be determined in a future study. Allograft monocytes can suppress T-cell proliferation in a dose-dependent fashion, potentially protecting from GVHD effects.…”

Section: Discussionmentioning

confidence: 99%

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

DeCook

Thoma

Huneke

et al. 2012

We have recently shown that lymphocyte and monocyte recovery by day þ 100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days þ 15, þ 30, þ 60 and þ 100 with the outcomes. Multivariate analysis revealed that day þ 100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P ¼ 0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P ¼ 0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, Po0.001). No patient in cluster C had a day þ 100 AMC 4300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day þ 100 post fludarabine/melphalanconditioned allogeneic hematopoietic SCT may be at risk for poor outcomes.

“…That time to platelet engraftment was influenced by graft type and donor type has been previously reported, with PBSC grafts associated with faster platelet engraftment. 8 Prolonged platelet nadirs can increase morbidity and mortality during transplantation because of increased bleeding risk, and platelet transfusions themselves can be associated with allergic and immunologic reactions that can contribute to transplant-related morbidity and mortality. 12 It is now generally accepted that a safe transfusion threshold for platelets is 10 Â 10 9 /L.…”

Section: Discussionmentioning

confidence: 99%

“…In spite of advantages of umbilical cord blood in shortened stem cell procurement times and decreased GVHD incidence and severity, 6 most evidence indicates delayed platelet engraftment times and, in some cases, delayed time to neutrophil engraftment. 7 The significance of delayed neutrophil and platelet engraftment times on overall survival has been reported, 8 but the extent to which engraftment times are affected by demographic, therapeutic and other clinical factors is poorly understood. In this retrospective study of consecutive patients undergoing SCT at the University of Rochester, we assessed the relationship between platelet and neutrophil engraftment times and patient age, gender, donor source of stem cells, type of graft and the effect of conditioning regimen intensity.…”

Section: Introductionmentioning

confidence: 99%

Clinical factors affecting engraftment and transfusion needs in SCT: a single-center retrospective analysis

Liesveld

Pawlowski

Chen

et al. 2012

Successful utilization of SCT modalities often requires utilization of both red cell and platelet transfusions. In this retrospective evaluation of clinical factors affecting transplant engraftment and transfusion utilization at a single transplant center in 505 patients from 2005 through 2009, we found that graft type, donor type and the conditioning regimen intensity significantly affected both the neutrophil engraftment time (Po0.001) and the platelet engraftment time (Po0.001). SCT patients required an average of 6.2 red cell units, and 7.9 platelet transfusions in the first 100 days with a wide s.d. Among auto-SCT patients, 5% required neither RBC nor platelet transfusions. Some reduced-intensity transplants were also associated with no transfusion need, and in allogeneic transplants, conditioning regimen intensity was positively correlated with platelet transfusion events as assessed by multivariate analysis. Other patient characteristics such as gender, graft type, donor type, underlying disease and use of TBI were all independently associated with transfusion needs in SCT patients. Further studies are required to understand the means to minimize transfusions and potential related complications in SCT patients.