Platelet Transfusion Refractoriness Pre-Allograft Is Associated with Higher Rates of Platelet Non-Engraftment and Graft Failure in Adult Allogeneic Haematopoietic Stem Cell Transplantation for Haematological Malignancies

Introduction

Platelet transfusion refractoriness (PTR) is relatively common in patients undergoing treatment for haematological malignancies. Alloimmunisation to either human leucocyte antigens (HLA) or human platelet specific antigens (HPA) can be demonstrated in up to 20% of cases. Recent data suggests that PTR may be associated with increased risk of non-engraftment following allogeneic haematopoietic progenitor cell transplantation (HPCT). We aimed to review the outcome of patients with PTR undertaking HPCT at our institution.

Methods:

All adults undertaking allogeneic HPCT for haematological malignancy at our institution between January 2008 and December 2013 were identified from an institutional database. This list was then correlated with records for special platelet support provided by the ARCBS for patients with PTR. Incidence of platelet engraftment, defined as the first of five consecutive days of transfusion-independent platelet counts >20 x10⁹/L, time to platelet engraftment and graft failure or rejection was then compared between those patients undertaking HPCT without prior PTR versus those patients with prior PTR. All grafts were T-cell replete; syngeneic and umbilical cord blood transplants were excluded.

Results

In total 480 patients underwent HPCT for haematological malignancy during the time period under review; 28 (6%) had PTR prior to HPCT and 452 did not. Of patients with PTR, 20/28 (71%) had demonstrable alloimmunisation due to anti HLA antibodies (n=20) or both anti-HLA and anti-HPA (n=1).Median age was identical for both the non-PTR vs PTR group respectively (50yrs; p=NS). Compared to the non-PTR group, the PTR group included a significantly greater proportion of AML diagnoses (75% vs 43%; p=.001), a non-significant increase in use of myeloablative conditioning (57% vs 40%; p=0.08) and increased use of unrelated donors (79% vs 59%; p=0.05). Although platelet engraftment occurred significantly less frequently in PTR patients (n=23, 82% vs n=431, 95%; p=0.01), time to platelet engraftment was similar between groups (median 20days, range 13-46 vs 18days, range 1-165 for PTR vs non-PTR groups respectively; p=0.24). Interestingly, of the 26 patients who failed to engraft platelets, 92% suffered early severe complications post-HPCT (multi-organ failure; severe sepsis; acute GVHD; diffuse alveolar haemorrhage), with only 2 patients (8%) suffering graft rejection; both of these patients were previously PTR. Risk of graft rejection was significantly associated with prior PTR (7% vs 0% respectively; p=0.003).

Conclusion:

PTR pre-HPCT is associated with significantly greater risk of graft rejection and non-platelet engraftment compared to patients without PTR. Early complications post-HPCT also appears to be associated with risk of platelet non-engraftment, irrespective of prior PTR or not.