Intensity of endogenous thrombocytopenia after autologous stem cell transplantation in patients prophylactically transfused with platelets.

BACKGROUND AND OBJECTIVES: Large clinical trials have demonstrated that some patient groups with hypoproliferative thrombocytopenia benefit from prophylactic platelet transfusions, while in others, a therapeutic transfusion regimen might be sufficient. The remaining capacity to generate endogenous platelets might be helpful to select the platelet transfusion regimen. We assessed whether the recently described method of digital droplet polymerase chain reaction (PCR) can be used to assess the endogenous platelet levels in two groups of patients undergoing high-dose chemotherapy with autologous stem cell transplantation (ASCT). MATERIALS AND METHODS: Multiple myeloma (n = 22) patients received high-dose melphalan alone (HDMA); lymphoma patients (n = 15) received BEAM or TEAM (B/TEAM) conditioning. Patients with a total platelet count <10 G/L received prophylactic apheresis platelet concentrates. Daily endogenous platelet counts were measured by digital droplet PCR for at least 10 days post-ASCT. RESULTS: Post-transplantation B/TEAM patients received their first platelet transfusion on average 3 days earlier than HDMA patients (p < 0.001) and required about twofold more platelet concentrates (p < 0.001). The endogenous platelet count fell ≤5 G/L for a median of 115 h (91-159; 95% confidence interval) in B/TEAM-treated patients compared to 12.6 h (0-24) (p < 0.0001) in HDMA-treated patients. Multivariate analysis confirmed this profound effect of the high-dose regimen (p < 0.001). The CD-34+ -cell dose in the graft was inversely correlated with the intensity of endogenous thrombocytopenia in B/TEAM-treated patients. CONCLUSION: Monitoring endogenous platelet counts detects the direct effects of myelosuppressive chemotherapies on platelet regeneration. This approach may help to develop a platelet transfusion regimen tailored to specific patient groups.

Efficacy of UVC-treated, pathogen-reduced platelets versus untreated platelets: a randomized controlled non-inferiority trial.

Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UVPlatelets, a novel UVC light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, noninferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. Primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and perprotocol analyses were 18.2% (95% confidence interval [CI]: 6.4%; 30.1) and 18.7% (95% CI: 6.3%; 31.1%), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (The German Clinical Trials Register number: DRKS00011156).

Platelet engraftment after allogenic stem cell transplantation is monitored by digital polymerase chain reaction without interference by platelet support.

Platelet engraftment after allogeneic hematopoietic stem cell transplantation is conventionally monitored by daily platelet counts. Platelet transfusions are frequently required and obscure the detection of platelet engraftment. Digital polymerase chain reaction (ddPCR) of mitochondrial DNA isolated from platelets reliably quantifies circulating platelets derived from the stem cell graft and allows us to distinguish them from transfused single-donor apheresis platelets. In a feasibility study, consecutive daily peripheral blood samples from day 7 to day 20 after transplantation were analyzed by ddPCR in 22 patients after allogeneic transplantation. Platelet engraftment according to ddPCR was defined as the third of at least 3 consecutive days of increasing levels exceeding 1000/µL endogenous platelets. Platelet counts were also assessed according to the engraftment cri`teria of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the European Society for Blood and Marrow Transplantation (EBMT). Out of the 22 patients, five did not achieve platelet engraftment within 20 days by any of the predefined criteria. A subgroup of nine patients did show platelet engraftment by all three definitions. In five patients, engraftment was detectable according to ddPCR and EBMT, whereas in three patients, platelet engraftment within 20 days was only confirmed by ddPCR. The detailed findings suggest that the day of platelet engraftment according to the EBMT criteria closely reflected the ddPCR detection of transplantation-derived platelets. The results from this feasibility study demonstrate that ddPCR offers a sensitive approach to detect platelet engraftment reliably and without interference from the individual noise of platelet counts due to platelet transfusions.