Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft‐versus‐host disease, donor type, cytomegalovirus infections and cell dose

Abstract

Platelet recovery after allogeneic haemopoietic stem cell transplant (HSCT) and predictive factors were analysed in 342 patients with haematological malignancies. All patients were prepared with cyclophosphamide plus total body irradiation, and received an unmanipulated HSCT from an HLA‐identical sibling (n = 270), a matched unrelated donor (n = 67) or an identical twin (n = 5). The source of stem cells was peripheral blood (n = 15) or bone marrow (n = 327). Graft‐vs.‐host disease (GvHD) prophylaxis consisted of cyclosporin A with or without methotrexate. The proportion of patients with < 50 × 109/l platelets on d +50, d +100, d +200 and d +365 after HSCT was 26%, 27%, 14% and 11% respectively. Thrombocytopenia was independent of the degree of complete donor chimaerism. Four variables were predictive of platelet recovery: donor type, acute GvHD, cytomegalovirus (CMV) infection and number of cells infused at transplant. Recipients of an unrelated graft had lower platelet counts (49 × 109/l) on d +50 than identical sibling grafts (108 × 109/l) (P < 0·001) and twin grafts (149 × 109/l) (P < 0·001). Patients with GvHD grades 0, I, II, III and IV had significantly different platelet counts on d +50 (153 × 109/l, 102 × 109/l, 85 × 109/l, 32 × 109/l and 22 × 109/l; P < 0·001) and thereafter. Thrombocytopenia was more frequent in patients with high‐level CMV antigenaemia (> four positive cells/2 × 105) (P < 0·0001) and in patients who received a low cell dose at transplant (≤ 4·1 × 108/kg) (P = 0·009). Platelet counts predicted transplant‐related mortality (TRM) and were higher at all time intervals in patients surviving the transplant. Patients with grade II GvHD and > 50 × 109/l platelets had a lower TRM than patients with grade II GvHD and ≤ 50 × 109/l platelets (14% vs. 40%, P < 0·0001). In conclusion, (i) a significant proportion of allogeneic HSCT recipients are thrombocytopenic long‐term, irrespective of complete donor chimaerism, (ii) thrombocytopenia identifies patients at greater risk of lethal complications, and (iii) platelet recovery is influenced by GvHD, donor type, CMV infections and cell dose, not by stem cell source or other patient–disease‐related variables.

Disease stage stratified effects of cell dose in unrelated BMT for hematological malignancies: a report from Japan marrow donor program

“…7,8,12,32 However, no significant effects of cell dose on NRM rates were observed in our study. To address this discrepancy, we performed a further analysis on causes of NRM according to cell dose, which showed no significant differences in the proportions of deaths from infection both in children and adults.…”

Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover

“…24,25 Taken together with the trend towards a high frequency of megakaryocytic hypoplasia in SCT recipients with thrombocytopenia, these data suggest that incomplete recovery of platelet production is one of the major causes of prolonged thrombocytopenia in SCT recipients. In this regard, the number of hematopoietic stem cells transplanted is reported to be important for platelet recovery after SCT, 26 but there was no difference in the number between patients with and without thrombocytopenia in our series of patients.…”

Serum cholinesterase is an early and sensitive marker of graft-versus host-disease (GVHD) and transplant-related mortality (TRM)

“…9 This finding suggests that, although different GVHD grades identify patients with different risk of TRM, 6 there is a heterogeneity of alloreactivity which is not picked up by the classical or revised GVHD scoring system. 6,10 In addition we lack an objective laboratory marker, with the exception of bilirubin for liver GVHD, and the clinical scoring of acute GVHD may differ significantly from one observer to another.…”