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Exploration of risk factors of platelet transfusion refractoriness and its impact on the prognosis of hematopoietic stem cell transplantation: a retrospective study of patients with hematological diseases
Song, X., Qi, J., Li, X., Zhou, M., He, J., Chu, T., Han, Y.
Platelets. 2023;34(1):2229905
Abstract
Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p < .001) and JAK mutation (OR = 17.32, p = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis. What is the context?Platelet transfusion refractoriness is a critical issue, and it greatly increases bleeding risks and hospitalization costs.Patients with hematological diseases tend to develop PTR.PTR results from immune and nonimmune factors and the latter account for 80–90%.At present, there are few studies focused on the inducing factors of PTR, and the specific mechanism is not clear.What is new?In this study, we investigated 108 patients with hematological disorders who received allogeneic HSCT from January 2019 to December 2020.We found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases.PTR had a passive effect on the prognosis of patients after HSCT, as indicated by worse OS and a trend toward lower platelets after transplantation.PTR might affect megakaryocyte reconstitution after transplantation.What is the impact?This study provides evidence that hematological patients with splenomegaly should be alert to the occurrence of PTR, which often indicates a worse prognosis of transplantation.Spleen reduction and JAK inhibitors in the treatment of PTR are worth exploring.AbbreviationsPLT: platelets; PTR: platelet transfusion refractoriness; HSCT hematopoietic stem cell transplantation; OR: odds ratio; HR: hazard ratio; CI: confidence interval; IQR: interquartile range; SD: standard deviation; HLA: human leukocyte antigen; HPA: human platelet antigen; OS: overall survival; RFS: relapse free survival; PI: post-transfusion increment; PPR: percentage platelet recovery; CCI: corrected count increment; ICU: intensive care unit; AA: aplastic anemia; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; ALL: acute lymphocytic leukemia; CML: chronic myeloid leukemia; CMML chronic myelomonocytic leukemia; MPN: myeloproliferative neoplasm; SI: splenic irradiation; Abs: antibodies; CR: complete remission; DAC: decitabine; GVHD graft-versus-host disease; BM: bone marrow; PB: peripheral blood. eng
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Intensity of endogenous thrombocytopenia after autologous stem cell transplantation in patients prophylactically transfused with platelets
Voß, A., Doescher, A., Kapels, H. H., Seltsam, A., Greinacher, A., Metzner, B., Müller, T. H.
Vox sanguinis. 2023
Abstract
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.
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[Incidence and clinical significance of platelet transfusion refractoriness after allogeneic hematopoietic stem cell transplantation in patients with chronic myelomonocytic leukemia]
Zhao, C., Zhao, X. S., Wang, Y., Yan, C. H., Xu, L. P., Zhang, X. H., Liu, K. Y., Huang, X. J., Sun, Y. Q.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2022;43(9):738-744
Abstract
Objective: To retrospectively analyze the incidence and clinical significance of platelet transfusion refractoriness (PTR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) . Methods: A cohort of 55 CMML patients received allo-HSCT at Peking University Institute of Hematology during 2004-2021 were retrospectively assessed. The incidence of PTR within 30 days after allo-HSCT was retrospectively analyzed, and the impact on clinical outcomes and bleeding event were compared between patients with platelet transfusion refractoriness (PTR) or effective platelet transfusion (EPT) . Results: The incidence of PTR after allo-HSCT in CMML patients was 25.5% (14/55) . PTR patients had a lower rate of platelet engraftment than EPT patients (28.6% vs 100%) , and the median time of engraftment was 67 (33-144) days and 21 (9-157) days respectively (P<0.010) . There was no significant difference between two groups in acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) (P=0.183, P=0.455) . After following-up a median of 684 (24-3978) days, the 1-year overall survival (OS) and 1-year leukemia free survival (LFS) in PTR and EPT patients were (35.4±13.9) % vs (75.1±7.8) % (P=0.037) and (28.1±13.3) % vs (65.3±8.2) % (P=0.072) , respectively. The transplant-related mortality (TRM) were (48.2±2.4) % and (9.0±0.25) %, respectively (P=0.009) . Bleeding events occurred in five patients (35.7%) of PTR and 2 patients (4.9%) of EPT (P=0.009) . Conclusion: In CMML patients with allo-HSCT, the incidence of PTR is 25.5%, which was associated with delayed platelet engraftment, increased bleeding events, inferior OS and increased TRM.
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[The Effect of Immunized Platelet Transfusion Refractoriness on Allo-HSCT Patients with Malignant Hematological Diseases]
Zuo, Y. L., Zhai, J. P., Li, Y., Jiang, M., Cui, Q. Y., Tang, X. W., Zhao, Y. M., Zhang, J. M.
Zhongguo shi yan xue ye xue za zhi. 2021;29(6):1923-1928
Abstract
OBJECTIVE To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients. METHODS The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34(+) cells, transplant prognosis, and so on. RESULTS In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P<0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α<0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P<0.01), while the percentage of ABO matching was significantly higher (α<0.0125). CONCLUSION The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.
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Comparison of a therapeutic platelet transfusion strategy to a prophylactic platelet transfusion strategy in autologous stem cell transplant (ASCT), a single centre experience
Savoia, C., McKeough, N., Hickey, B., Cochrane, T.
Bone marrow transplantation. 2021
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Mitigation strategies for anti-D alloimmunization by platelet transfusion in haematopoietic stem cell transplant patients: a survey of NCCN((R)) centres
Poston, J. N., Sugalski, J., Gernsheimer, T. B., Marc Stewart, F., Pagano, M. B.
Vox sanguinis. 2020
Abstract
BACKGROUND AND OBJECTIVES D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT. METHODS AND MATERIALS To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network((R)) (NCCN((R)) ). RESULTS Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age. CONCLUSION There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients.
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The assessment of platelet function by thromboelastometry as a point-of-care test to guide Intercept-treated platelet support in hemato-oncological patients and hematopoietic stem cell transplantation recipients
Leitner, G. C., Ho, M., Tolios, A., Hopfinger, G., Rabitsch, W., Wohlfarth, P.
Transfusion. 2020
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Abstract
BACKGROUND Pathogen inactivation (PI) techniques for platelet concentrates (PCs) are one of the latest innovations to improve blood safety and reduce the risk of transfusion-transmitted infections (TTIs). An impaired function and in vivo recovery of platelets as well as an increased PC demand are concerns regarding these techniques. The intent of this study was to evaluate the hemostatic effect of PCs treated with the Intercept System by thromboelastometry (TEM) and to assess the clinical validity of its results in comparison to post-transfusion increase (PTI) and corrected count increment (CCI). STUDY-DESIGN AND METHODS This prospective-observational study included 47 patients (m:f = 25:22; median age: 54 years [21-70]) of our Bone Marrow Transplantation unit with hemato-oncological malignancies transfused with Intercept-treated PCs. Serial TEM measurements were performed just before and 1 hour after PC transfusion and were analyzed for their correlation with PTI and CCI as well as for clinical variables. RESULTS The majority of our patients had received a hematopoietic stem cell transplantation (HSCT) (n = 41; 87%). In median 9 (1-50) PCs were transfused. Serial TEM, PTI, and CCI measurements were available for 150 transfusion episodes. The median platelet dose transfused was 2.65 x 10(11) /unit (1.8-6). The median CCI was 9.250 (0-28.000). We observed a significant improvement in TEM parameters (p < 0.05) after transfusion of PI PCs, which did not mandatory correlate with the 1-hour PTI and CCI. CONCLUSION Serial TEM measurements indicate the hemostatic effect of Intercept-treated PCs. The 1-hour PTI and CCI may not appropriately reflect the in vivo function of platelets after PI PC transfusion.
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Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation
Seike, K., Fujii, N., Asano, N., Ohkuma, S., Hirata, Y., Fujii, K., Sando, Y., Nakamura, M., Naito, K., Saeki, K., et al
Transfusion. 2020
Abstract
BACKGROUND Cross-matched platelet (cross-matched PLT) transfusion is effective for immune-mediated platelet transfusion refractoriness (PTR), but is more costly and time-consuming for physical cross-match than using standard PLT units. Recent studies have reported the utility of human leucocyte antigens (HLA) virtual cross-matched PLT (HLA-matched PLT) that is defined as HLA-A/B matched or no antibody against donor-specific antigen. Here, we evaluated the effect of HLA-matched PLTs for PTR in post hematopoietic stem cell transplant (HSCT) recipients. STUDY DESIGN AND METHODS Our study included a total of 241 PLTs in 16 patients who underwent HSCT at Okayama University Hospital between 2010 and 2017, receiving either HLA-matched or cross-matched PLTs. We calculated the 24-hour corrected count increments (CCI-24) to evaluate the effect of PLTs. A CCI-24 ≥ 4500 was considered to be a successful transfusion. RESULTS We analyzed 139 cross-matched PLTs and 102 HLA-matched PLTs. In the immune-mediated PTR, the rate of successful transfusion was 60.5% for cross-matched PLT and 63.4% for HLA-matched PLT (p = 0.825). On the other hand, the median CCI-24 for cross-matched PLT transfusions and HLA-matched PLT transfusions were 1856 and 5824 (p < 0.001), with a success rate of 28.1 and 54.1% in cases with non-immune-mediated PTR, respectively (p = 0.001). CONCLUSION The effectiveness of HLA-matched PLT is not inferior to cross-matched PLT. This result indicates that physical cross-match can be omitted in post HSCT PTR.
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Combination treatment of rituximab and donor platelets infusion to reduce donor-specific anti-HLA antibodies for stem cells engraftment in haploidentical transplantation
Zhang, R., He, Y., Yang, D., Jiang, E., Ma, Q., Pang, A., Zhai, W., Wei, J., Feng, S., Han, M.
Journal of clinical laboratory analysis. 2020;:e23261
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Abstract
BACKGROUND Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) in recipients is a risk factor for donor stem cell graft failure in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), and the treatment to reduce the levels of DSAs is not unanimous. This study was to analysis the role of DSAs for stem cell engraftment and to discuss the effective treatment to reduce DSAs in haplo-HSCT. METHODS We retrospectively evaluated the levels of DSAs and the effect of the combination treatment of rituximab and donor platelets (PLTs) for donor stem cell engraftment in haplo-HSCT patients from June 2016 to March 2018 at our center. RESULTS Nine patients (11.5%) out of the total 78 patients were DSAs-positive and multivariate analysis revealed DSAs was the only factor that affected engraftment. Seven out of the 9 DSAs (+) patients received therapy: Four had antibodies against donor HLA class I (HLA-I) antigens and were administered two therapeutic amounts of donor apheresis platelets (platelet count approximately 3-5 x 10(11) ) before donor stem cell infusion and the other three patients received a combination therapy of donor apheresis platelets and rituximab due to the antibodies against both donor HLA-I antigens and HLA class II (HLA-II) antigens. All the seven patients achieved donor stem cell engraftment successfully, and the DSAs levels decreased rapidly after transplantation. CONCLUSIONS DSAs is an important factor affecting engraftment in haplo-HSCT. Donor platelet transfusion is one simple and effective treatment for HLA-I DSAs, and a combination therapy should be administered if patients have both HLA-I and HLA-II antibodies.
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Refractory Thrombocytopenia is a Valid Early Diagnostic Criteria for Hepatic Veno-Occlusive Disease in Children
Embaby, M. M., Rangarajan, H. G., Abu-Arja, R., Auletta, J. J., Stanek, J., Pai, V., Nicol, K. K., Bajwa, R. S.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
We compared the incidence of refractory thrombocytopenia (RT) and platelet transfusion requirements (PTR) in 35 children who developed VOD with 35 matched controls who underwent HSCT but did not develop VOD. RT developed in 100% of the VOD patients, at a median of 8 days before VOD diagnosis, as compared to 71.5% of the control group. VOD patients required more platelets transfusions than controls (median PTR 6.9 ml/kg (range: 0.57-17.59) vs. 3.57 ml/kg (range: 0-14.63) in the control group with the difference being statistically significant (P < 0.0001). Numbers of days with platelet requirement, were significantly higher for VOD patients as compared to controls, (median % of days 68% vs. 39%, P=< .0001). The PTR peaked at approximately 12 mL/kg/day, 2 days before VOD diagnosis, whereas the PTR in the control population was 5 mL/kg/day. The positive predictive value (PPV) of developing VOD was 88.9% (95% CI: 66.5-97%) in patients who were given >7ml/kg/day of platelets during at risk period of days +3 to +13 after transplant. For patients who got >8ml/kg/day pf platelets, the PPV of developing VOD was 86.7% (95%CI: 61.2 -96.4%). There was no difference in the PTR in patients with mild to moderate VOD as compared to those with severe VOD, however PTR was higher in patients whose VOD did not resolve. The median, average, daily PTR after the diagnosis of VOD in 17 patients who got defibrotide as compared to those who did not get defibrotide was 6.04 ml/kg and 5.72 ml/kg respectively and the difference was not statistically significant (p=0.56). On univariate and multivariate analysis use of intravenous immunoglobulin (IVIG) was significantly associated with VOD (p=0.0088), however use of IVIG was not significantly associated with fatal VOD. In conclusion RT occurs in 100% of patients at a median of 8 days before VOD diagnosis. VOD should be suspected in any patient with RT after the exclusion of other causes of consumptive thrombocytopenia especially if they are needing >7ml/kg/day of platelets.