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1.
Lack of RBC transfusion independence by Day 30 following allogeneic hematopoietic stem cell transplant strongly predicts inferior survival and high non-relapse mortality in acute myeloid leukemia patients
Yuan, S., Yang, D., Nakamura, R., Al Malki, M. M., Salhotra, A., Afkhami, M., Wang, S.
Transfusion. 2024
Abstract
BACKGROUND Studies have suggested that acute myeloid leukemia (AML) patients with incomplete hematologic recovery undergoing allogeneic stem cell transplantation (allo-HSCT) had inferior overall survival (OS). STUDY DESIGN AND METHODS This single-center, retrospective study of AML patients evaluated the relationship between red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 30 days and long-term outcomes after allo-HSCT through multivariate analyses. RESULTS A total of 692 AML patients received peripheral blood stem cells (89.2%), marrow (5.6%), or umbilical cord (5.2%) from matched related (37.4%), unrelated (49.1%), or haploidentical (8.2%) donors in 2011-2017. Transfusion requirements during the first 30 days for RBC (89.5% transfused, median 3, range 1-18 units) or PLT (98.2% transfused, median 6, range 1-144 units) were variable. By Day 30, 56.7% (95% confidence interval [CI]: 52.8-60.3%) and 86.1% (95% CI: 83.2-88.5%) had achieved RBC and PLT transfusion independence, respectively. Median follow-up among survivors (n = 307) was 7.1 years (range: 2.7-11.8). Lack of RBC transfusion independence by Day 30 was strongly and independently associated with worse 5-year OS (39.2% vs. 59.6%, adjusted hazard ratio [HR] 1.83, 95% CI: 1.49-2.25), leukemia-free survival (35.8% vs. 55.5%, HR = 1.75, 95% CI: 1.43-2.14), and NRM (29.7% vs. 13.7%, HR = 2.05, 95% CI: 1.45-2.89) (p < .001). There was no difference in relapse rates among patients who achieved or did not achieve RBC (p = .34) or PLT (p = .64) transfusion independence. CONCLUSION Prolonged RBC dependence predicted worse survival and NRM rates, but not increased relapse. Posttransplant surveillance of such patients should be adjusted with more attention to non-relapse complications.
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2.
Impact of Iron overload and Iron Chelation with deferasirox on outcomes of patients with severe aplastic anemia after allogeneic hematopoietic stem cell transplantation
Pan, T., Ji, Y., Liu, H., Tang, B., Song, K., Wan, X., Yao, W., Sun, G., Wang, J., Sun, Z.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Patients suffering from severe aplastic anemia (SAA) need frequent blood transfusions during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these transfusions can result in an excess of iron in the body tissues, which can negatively impact the success of the transplant. OBJECTIVES This study aimed to examine the impact of pre-transplant iron overload (IO) on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA). It also investigated whether iron chelation (IC) therapy was necessary to enhance transplantation outcomes in SAA patients by providing guidelines for determining when excess iron should be chelated. STUDY DESIGN The study consisted of two parts: Cohort 1, which was retrospective and conducted from April 2012 to December 2018, divided SAA patients receiving their first allo-HSCT into two groups based on their pre-transplant serum ferritin (SF) levels: the iron overload (IO) group (SF >1000 ng/ml, n=17) and the non-IO group (SF ≤ 1000 ng/ml, n=48). Cohort 2 was a prospective clinical trial conducted from January 2019 to July 2020. It involved SAA patients diagnosed with IO who were treated with iron chelation (IC) therapy using deferasirox (DFX) at a dose of 10-30 mg/kg. Patients were separated into two groups based on their pre-transplant SF levels: the IC success (IC(success)) group (SF ≤ 1000 ng/ml, n=18) and the IC failure (IC(failure)) group (SF >1000 ng/ml, n=28) groups. All participants were evaluated for the correlation between pre-transplant SF levels and transplantation outcomes. A P-value of less than 0.05 was considered statistically significant. RESULTS There was no significant difference in the speed of engraftment for the three lineages or in the incidence of 100-day grade II-IV acute graft-versus-host disease (aGVHD), grade III-IV aGVHD, or 3-year chronic GVHD between the two groups in both cohorts. However, in cohort 1, it was noteworthy that 1-year OS (83.3% vs. 41.2%, p < 0.001) and 3-year OS (83.3% vs. 35.3%, p < 0.001) were significantly worse in the IO group. Furthermore, 180-day TRM (14.6% vs. 47.1%, p = 0.005) and 1-year TRM (16.7% vs. 52.9%, p = 0.002) were significantly higher in the IO group. The IO group was significantly associated with inferior 3-year OS in both univariate and multivariate analyses. In cohort 2, it was found that 1-year OS (42.9% vs. 88.9%, p = 0.003) and 3-year OS (42.9% vs. 83.3%, p = 0.007) were significantly better in the IC(success) group, while 180-day TRM (11.1% vs. 39.3%, p = 0.040) and 1-year TRM (11.1% vs. 57.1%, p = 0.003) were significantly lower in the IC(success) group. These differences were confirmed in both univariate and multivariate analyses. CONCLUSIONS The study involving two cohorts showed that pre-HSCT iron overload has a negative impact on transplantation outcomes in SAA patients. Chelating excess iron with a serum ferritin level below 1000 ng/ml was found to be necessary and could potentially improve the outcomes.
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3.
Transfusion Burden in Allogeneic Hematopoietic Stem Cell Transplantation over Time: Experience from a Single Institution
Solves, P., Marco-Ayala, J., Sanz, MÁ, Gómez-Seguí, I., Balaguer-Roselló, A., Facal, A., Villalba, M., Montoro, J., Sanz, G., de la Rubia, J., et al
Journal of clinical medicine. 2023;12(10)
Abstract
INTRODUCTION Transfusion plays a main role in supportive treatment for patients who receive an allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we compare the transfusion requirements of patients undergoing different modalities of HSCT according to different time periods. The objective is to assess the evolution of HSCT transfusion requirements over time, from a single institution. METHODS The clinical charts and transfusion records of patients who underwent HSCT of different modalities at La Fe University Hospital during a twelve-year period were reviewed (2009-2020). For analysis, we divided the overall time into three periods: 1 from 2009 to 2012, 2 from 2013 to 2016 and 3 from 2017 to 2020. The study included 855 consecutive adult HSCT 358 HLA-matched related donors (MRD), 134 HLA-matched unrelated donors (MUD), 223 umbilical cord blood transplantation (UCBT) and 140 haploidentical transplants (Haplo-HSCT). RESULTS There were no significant differences in RBC and PLT requirements or transfusion independence among the three time periods for MUD and Haplo-HSCT. However, the transfusion burden increased significantly for MRD HSCT during the 2017-2020 period. CONCLUSION despite HSCT modalities having evolved and changed over time, overall transfusion requirements have not significantly decreased and continue to be a cornerstone of transplantation-supportive care.
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4.
Evaluation of Dengue, Zika virus, and Chikungunya virus transmission by blood components in recipients of haematopoietic stem cell transplantation
de Oliveira, F. N., Ferreira, S. C., Nishiya, A. S., Mendrone-Junior, A., Batista, M. V., Rocha, V., Costa, S. F.
Transfusion medicine (Oxford, England). 2023
Abstract
BACKGROUND Brazil has a high prevalence of arboviruses, especially Dengue (DENV), Zika (ZKV), and Chikungunya (CHKV). OBJECTIVES To study the risk of DENV, ZKV, and CHKV transmission by blood components in the haematopoietic stem cell transplantation (HSCT) population. METHODS Prospective cohort of HSCT recipients and donors performed at the Hospital das Clinicas da FMUSP, São Paulo-Brazil. Patients were evaluated by serology and RT-PCR for DENV, ZKV, and CHKV pre-transplantation and once a week until neutrophil grafting. In positive cases (positive RT-PCR and/or serology conversion), an investigation was carried out on the blood components that the patient received to evaluate the possibility of it being transfusion transmitted. RESULTS A total of 93 patients were included during the study period. The mean age was 52 years with a predominance of males (56.9%). We considered five (5.3%) DENV cases positive by seroconversion in our study. One patient had IgM seroconversion and the other four presented IgG seroconversion to DENV. In the investigation of the blood components, 145 individual samples were analysed. None of the investigated blood components showed a positive RT-PCR. CONCLUSION We observed a low prevalence of DENV, ZKV, and CHKV in HSCT donors and recipients by serology and RT-PCR, and no case of blood transfusion transmission by RT-PCR.
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5.
Iron overload following hematopoietic stem cell transplantation: Prevalence, severity and management in children and adolescents with malignant and non-malignant diseases
Cattoni, A., Capitoli, G., Casagranda, S., Corti, P., Adavastro, M., Molinaro, A., Gennaro, F. D., Bonanomi, S., Biondi, A., Galimberti, S., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Iron overload (IOL) is a frequently reported complication following hematopoietic stem cell transplantation (HSCT) which has been extensively assessed in the field of hemoglobinopathies, but has not been thoroughly characterized after HSCT in pediatric malignancies. OBJECTIVES Our aim was to assess prevalence, severity, risk factors and management of IOL, as defined by means of biochemical (serum ferritin) and radiological tools (T2*-MRI), in a cohort of pediatric patients transplanted for either malignant or benign diseases. STUDY DESIGN Monocentric, retrospective, observational study. All the 163 patients alive and in continuous remission 24 months after HSCT, out of the 219 consecutive children and adolescents transplanted at our Institution between 2012 and 2018, were included in the study. IOL was classified into four categories, i.e. absent, mild, moderate and severe. RESULTS Of the 163 patients, 73% had some degree of IOL, which was mild, moderate and severe in 37%, 29% and 7%, respectively. Moderate/severe IOL was more frequent among patients diagnosed with a malignant versus benign disease (43% vs 19%; p 0.0065). Ferritin trend lines showed a "bell-shaped" distribution, with the highest levels being recorded during the first 6 months after HSCT, followed by a spontaneous reduction. Both pre-HSCT (1659 versus 617 ng/mL, p<0.001) and maximum post-HSCT (2473 ng/mL versus 1591 ng/mL, p<0.001) median ferritin levels were statistically higher among patients with malignancies. Radiological assessment of IOL confirmed a more severe degree in malignant compared to benign disorders (median T2*-MRI 4.20 msec, IQ: 3.0-6.40 versus 7.40, IQ: 4.90-11.00, respectively - p 0.008). T2* levels were associated with the number of transfusions performed (p 0.0006), with a steeper drop in T2* values for the first 20 transfusions and a milder slope subsequently. T2* and ferritin values showed a statistically significant negative exponential relationship (p<0.0001), though ferritin levels ≥1000 ng/mL showed a poor specificity (48%) and positive predictive value (53%) in discriminating moderate-to-severe from absent-mild IOL as assessed by T2*-MRI, but high sensitivity (92%) and negative predictive value (91%). In a multivariable model, >20 transfusions (OR 4.07, 95% CI 1.61-10.68, p 0.003) and higher pre-HSCT ferritin levels (p<0.001) were associated with the risk of developing moderate-to-severe IOL. A sibling donor (OR 0.29, 95% CI 0.10-0.77, p 0.015) and a non-malignancy (OR 0.27, 95% CI 0.08-0.82, p 0.026) were protective factors. Phlebotomies (66%), low-dose oral chelators (9%) or a combined approach (25%) were started at a median of 12 months after HSCT in 78% of the patients with IOL. Six% of the patients treated exclusively with phlebotomies (median 14, significantly higher in patients >40 kg) discontinued them due to poor venous accesses, lack of compliance or hypotension, whereas 39% of patients treated with chelators developed mild renal or hepatic side effects which resolved upon tapering or discontinuation. CONCLUSIONS Patients with malignancies showed statistically higher pre- and post-HSCT ferritin levels and lower T2*. High ferritin recorded upon T2*-MRI showed unsatisfactory diagnostic accuracy in predicting IOL, thus, T2*-MRI should be regarded as a key element to confirm IOL after HSCT in patients with elevated ferritin levels. IOL treatment is feasible after HSCT.
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6.
Iron Chelation with Deferasirox suppresses the Appearance of LPI during Conditioning Chemotherapy prior to Allogeneic Stem Cell Transplantation
Essmann, S., Heestermans, M., Dadkhah, A., Janson, D., Wolschke, C., Ayuk, F., Kröger, N. M., Langebrake, C.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND During conditioning chemotherapy prior to allogeneic haematopoietic stem cell transplantation (HSCT) non-transferrin-bound iron and its chelatable form, labile plasma iron (LPI), regularly appear in the blood of patients at high levels of transferrin saturation (TfS). As these free iron species potentially favour infection and mediate transplant-associated toxicities, chelation therapy could be an approach to improve outcome after transplantation. However, data addressing iron chelation in the immediate peri-transplantation period are sparse. OBJECTIVE To investigate the influence of iron chelation with deferasirox during conditioning chemotherapy on the appearance of LPI, the incidence of infection and toxicities and its tolerability in the peri-transplantation period. STUDY DESIGN We conducted a single-center, prospective, observational study in 25 adult, iron-overloaded (serum ferritin > 1000 µg/l) patients with planned allogeneic HSCT after myeloablative, busulfan-based conditioning chemotherapy. Patients received iron chelation with deferasirox (14 mg/kg) from the start of conditioning until day 3 after transplantation. Iron parameters including LPI were obtained at chelator's trough level daily until d0 and on d4, d7 and d14. Data regarding infection (bacteraemia or invasive fungal disease) and toxicity as well as the tolerability of deferasirox was collected until the end of the follow-up period on d28. Data was analysed descriptively. RESULTS TfS levels exceeded 70 % in median on 6 days (4-10 days) and in 63.6 % (36.4-90.9 %) of the samples per patient. Although, in 19 of 25 patients (76 %) no elevated LPI values were detected during the intake of deferasirox despite high TfS levels. Only six patients (24 %) showed mildly increased LPI values (≤ 0.5 units) during the intake of deferasirox, three of whom presented with elevated LPI values before the start of conditioning. Deferasirox was well tolerated and no aggravation of toxicities was observed. Infection occurred in five patients (20 %), comprising three of the six patients with elevated LPI values despite chelation therapy. CONCLUSION In the present study, we demonstrate that iron chelation with deferasirox safely suppresses the appearance of LPI and might decrease the incidence of infection, while the impact on transplant-associated toxicities remains to be elucidated.
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7.
[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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8.
Efficacy and Safety of Iron Chelation Therapy After Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Thalassemia Patients: A Retrospective Observational Study
Kupesiz, F. T., Sivrice, C., Akinel, A., Kintrup, G. T., Guler, E., Kupesiz, A.
Journal of pediatric hematology/oncology. 2022;44(1):e26-e34
Abstract
BACKGROUND Studies on the increased body iron load in patients with thalassemia major have thoroughly demonstrated the problems caused by iron overload. In patients who undergo hematopoietic stem cell transplantation (HSCT) as curative therapy, iron overload continues long after transplantation. There are few pediatric studies on chelation therapy in the posttransplant period. In this study, we present the outcomes of our patients who received posttransplant oral chelation therapy. PATIENTS AND METHODS This retrospective observational study evaluated the outcomes of pediatric patients with thalassemia major who used oral chelation therapy after allogeneic HSCT at the Akdeniz University Pediatric Bone Marrow Unit between January 2008 and October 2019. RESULTS Deferasirox therapy was initiated in 58 pediatric patients who underwent HSCT for thalassemia. Pretreatment mean serum ferritin was 2166±1038 ng/mL. Treatment was initiated at a mean of 12±6.7 months after transplantation and continued for a mean of 15.7±11.5 months. At treatment discontinuation, the mean serum ferritin was 693±405 ng/mL and the mean reduction was -1472.75±1121.09 ng/mL (P<0.001 vs. posttreatment). Serum ferritin was below 500 ng/mL in 52% of the patients at treatment discontinuation. Manageable side effects such as nausea, vomiting, liver enzyme elevation, and proteinuria were observed in 17% of the patients, while one patient developed ototoxicity. CONCLUSIONS Deferasirox therapy effectively reduces iron overload in the posttransplant period. Studies evaluating the effects of early treatment on the graft may help to establish guidelines for posttransplant chelation therapy. Clear guidelines are needed regarding when to initiate and discontinue treatment.
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9.
Analysis of the variable factors affecting changes in the blood concentration of cyclosporine before and after transfusion of red blood cell concentrate
Uchida, M., Hanada, N., Yamazaki, S., Takatsuka, H., Imai, C., Utsumi, A., Shiko, Y., Kawasaki, Y., Suzuki, T., Ishii, I.
Journal of pharmaceutical health care and sciences. 2022;8(1):4
Abstract
BACKGROUND The blood concentration of cyclosporine (CyA) is frequently elevated following the transfusion of red blood cell concentrate (RCC) to patients after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to identify the variable factors affecting changes in the blood concentration of CyA before and after transfusion of RCC. METHODS We enrolled 105 patients (age, 5-66 years) who received both CyA and transfusion after HSCT. The ratio of the measurement after transfusion to the measurement before transfusion was calculated for the hematocrit and blood concentration/dose ratio of CyA (termed the HCT ratio and the CyA ratio, respectively). RESULTS The blood concentration/dose ratio of CyA was increased after transfusion compared with before transfusion (P < 0.001). The HCT ratio was significantly correlated with the CyA ratio (P = 0.23, P < 0.001). The HCT ratio, concomitant medication that could elevate CyA concentration after RCC transfusion, and difference in the alkaline phosphatase level between before and after transfusion (ΔALP) were explanatory variables associated with the variation in the CyA ratio. There was no correlation between the CyA concentration after transfusion and the change in the estimated glomerular filtration rate. CONCLUSIONS A change in the blood concentration/dose ratio of CyA was found to be associated with a change in the HCT, concomitant medication that could elevate CyA concentration after RCC transfusion, and ALP levels. If the HCT level rises significantly after RCC transfusion, clinicians and pharmacists should pay attention to changes in the blood CyA concentration.
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10.
Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with paroxysmal nocturnal hemoglobinuria
Nakamura, Y., Takenaka, K., Yamazaki, H., Onishi, Y., Ozawa, Y., Ikegame, K., Matsuoka, K. I., Toubai, T., Ueda, Y., Kanda, Y., et al
International Journal of Hematology. 2021;113(1):122-127
Abstract
The safety and efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) remain unclear. Therefore, we retrospectively analyzed the outcomes of 42 adult patients with PNH who underwent allogeneic HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median patient age was 32.5 years. The number of packed red cell (PRC) transfusions was < 20 times in 19 patients and ≥ 20 times in 16; 7 patients had missing data. Stem cell sources were bone marrow (N = 15) or peripheral blood (N = 13) from a related donor or bone marrow (N = 11) and cord blood (N = 3) from an unrelated donor. The cumulative incidence of neutrophil engraftment at day 40 was 81%. Six patients died before engraftment, and the 6-year overall survival (OS) was 74%. The OS of patients with < 20 pretransplant PRC transfusions was significantly higher than that of patients with ≥ 20 pretransplant PRC transfusions (95% vs. 63%; P < 0.05). Moreover, the OS of patients aged < 30 years was significantly higher than that of patients aged ≥ 30 years (90% vs. 59%; P < 0.05). Allogeneic HSCT for PNH could provide favorable survival; however, pretransplant transfusion burden and patient age should be considered when deciding the timing of allogeneic HSCT.