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1.
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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2.
Long-term effect of hematopoietic stem cell transplantation on the quality of life of patients with β-thalassemia major in Guangxi, China--A cross-sectional study
Zhai, L., Liu, Y., Huo, R., Pan, Z., Zhang, Y., Li, Z., Li, F., Fan, J., Wei, W.
Current stem cell research & therapy. 2022
Abstract
OBJECTIVE The purpose of our study was to compare the quality of life (QOL) of patients with hematopoietic stem cell transplantation (HSCT) for more than 2 years for β-thalassemia major (β-TM) with that of β-TM patients with conventional therapy (blood infusion and iron chelation) and that of the general population. METHODS This was a cross-sectional comparative study on the QOL of 225 β-TM patients treated with blood transfusion and iron-chelation therapy, 133 β-TM patients who had undergone HSCT or 270 age- and sex-matched healthy individuals from Guangxi, China. Child-self and parent-proxy reports of the PedsQL 4.0 Generic Core Scales were used to prospectively evaluate QOL. RESULTS The incidence of acute GVHD was 14.3% (grade III-IV in 4.5% of patients), and that of chronic GVHD was 3.8%. This was lower than that of previous studies since the inclusion of anti-thymocyte globulin(ATG)ATG. Patients who underwent transplantation from a voluntary donor had higher QOL scores and lower rates of acute GVHD, chronic GVHD and comorbidities than those receiving stem cell sources from an HLA mismatched related donor (haploidentical donor). Transplants with PBSCs or UCBT, PBSCT+BMT, BMT, or BMT+UCBT as stem cell sources did not have any impact on QOL. The QOL of β-TM patients was very similar to that of the general population. More complications (P<0.001), shorter posttransplantation time (P<0.001) and older age at HSCT (P=0.01) were associated with poorer child QOL (P=0.020). Additional analyses investigating QOL β-TM patients receiving conventional treatment with β-TM revealed poorer outcomes than the cohort of transplanted patients. CONCLUSION β-TM patients can be cured by HSCT and regain QOL as good as that of the general population. β-TM patients are suggested to undergo HSCT as soon as possible to avoid complications related to iron overload and blood infusion.
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3.
Outcome of iron reduction therapy in ex-thalassemics
Aboobacker, F. N., Dixit, G., Lakshmi, K. M., Korula, A., Abraham, A., George, B., Mathews, V., Srivastava, A.
PloS one. 2021;16(1):e0238793
Abstract
There is limited data on iron reduction therapy (IRT) after successful allogeneic haematopoietic stem cell transplantation (aHSCT) for patients with thalassemia major (TM). We present the long term outcome of IRT in 149 patients with TM who underwent aHSCT during January, 2001-December, 2012. The median age was 7 years (range:1-18) and 92 (61.7%) belonged to Pesaro class 3 with a median ferritin at aHSCT of 2480ng/ml (range:866-8921). IRT was reinitiated post-aHSCT at a median of 14 months (range:5-53) post aHSCT with phlebotomy alone in 10 (6.7%) patients or iron chelation alone in 60 (40.3%) patients while 79 (53%) were treated with the combination. Reduction in serum ferritin/month [absolute quantity (ng/ml/month) was as follows: 87 (range:33-195), 130 (range:17-1012) and 147 (range:27.7-1427) in the phlebotomy, chelation and combination therapy groups, respectively (p = 0.038). With a median follow up of 80 months (range:37-182), target ferritin level of <300ng/ml was achieved in 59(40%) while a level <500ng/ml was achieved in 88 patients (59%) in a median duration of 41 months of IRT (range: 3-136). Patients in class III risk category and higher starting serum ferritin levels (>2500ng/ml) were associated with delayed responses to IRT. Our data shows that IRT may be needed for very long periods in ex-thalassaemics to achieve target ferritin levels and should therefore be carefully planned and initiated as soon as possible after aHSCT. A combination of phlebotomy and iron chelators is more effective in reducing iron overload.
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4.
Pre-transplant donor-type red cell transfusion is a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants
Mehta, P., Ramprakash, S., Raghuram, C. P., Trivedi, D., Dhanya, R., Agarwal, R. K., Faulkner, L.
Annals of hematology. 2021
Abstract
ABO incompatibility is not a barrier to allogeneic stem cell transplant but may result in acute hemolytic reactions. As stem cell product manipulation is cumbersome, we are reporting the effectiveness and safety of donor-type red cell infusion as a method of reducing acute hemolytic reaction while using marrow as stem cell source. In major ABO-mismatched bone marrow transplants, manipulation of marrow product requires expertise and expensive equipment, which may not be readily available to transplant centers in low- and middle-income regions. The aim behind our study is to report a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants. We retrospectively analyzed 303 consecutive allogeneic bone marrow transplants (BMTs) for beta thalassemia major, between August 2015 and March 2020, with either major (n = 41) or bidirectional (n = 14) mismatches. When isohemagglutinin titers were 1:32 or higher, donor-type packed red blood cell was divided into 4 aliquots, irradiated and administered over 4 days at incremental volumes. Patients were observed for hemolytic reaction, and if no reaction, bone marrow was infused without manipulation. Out of 55 patients, 20 received donor-type blood infusion. Twelve patients showed evidence of mild hemolysis. None developed severe hemolytic or anaphylactic reaction. Titers were rechecked in 14 patients and all had reduction in titers, except for one. Our experience demonstrated that donor-type PRBC infusion is safe and effective in preventing acute hemolysis in major ABO-mismatched stem cell transplants even with bone marrow as graft source.
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5.
Quantification of Liver Iron Overload: Correlation of MRI and Liver Tissue Biopsy in Pediatric Thalassemia Major Patients Undergoing Bone Marrow Transplant
Bafna, V., Bhat, S., Raj, V., Badiger, S., Annapandian, V. M., Nataraj, K. S., Damodar, S.
Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion. 2020;36(4):667-673
Abstract
Determination of the magnitude of body iron stores helps to identify individuals at risk of iron-induced organ damage in Thalassemia patients. The most direct clinical method of measuring liver iron concentration (LIC) is through chemical analysis of needle biopsy specimens. Here we present a noninvasive method for the measurement of LIC in vivo using magnetic resonance imaging (MRI). Twenty-three pediatric Thalassemia major patients undergoing bone marrow transplantation at our centre were studied. All 23 patients had MRI T2* and R2* decay time for evaluation of LIC on a 1.5 Tesla MRI system followed by liver tissue biopsy for the assessment of iron concentration using an atomic absorption spectrometry. Simultaneously, serum ferritin levels were measured by enzymatic assay. We have correlated biopsy LIC with liver T2* and serum ferritin values with liver R2*. Of the 23 patients 11 were males, the mean age was 8.3 ± 3.7 years. The study results showed a significant correlation between biopsy LIC and liver T2* MRI (r = 0.768; p < 0.001). Also, there was a significant correlation between serum ferritin levels and liver R2* MRI (r = 0.5647; p < 0.01). Two patients had high variance in serum ferritin levels (2100 and 4100 mg/g) while their LIC was around 24 mg/g, whereas the difference was not seen in T2* MRI. Hence, the liver T2* MRI is a better modality for assessing LIC. Serum ferritin is less reliable than quantitative MRI. The liver T2* MRI is a safe, reliable, feasible and cost-effective method compared to liver tissue biopsy for LIC assessment.
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6.
Blood transfusion support for sickle cell patients during haematopoietic stem cell transplantation: a single-institution experience
De Santis, G. C., Costa, T. C. M., Santos, F. L. S., da Silva-Pinto, A. C., Stracieri, Abpl, Pieroni, F., Darrigo-Junior, L. G., de Faria, J. T. B., Grecco, C. E. S., de Moraes, D. A., et al
British journal of haematology. 2020
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7.
Human leukocyte antigen (HLA) class I antibodies and transfusion support in paediatric HLA-matched haematopoietic cell transplant for sickle cell disease
Nickel, R. S., Horan, J. T., Abraham, A., Qayed, M., Haight, A., Ngwube, A., Liang, H., Luban, N. L. C., Hendrickson, J. E.
British journal of haematology. 2019
Abstract
The relevance of donor-specific human leukocyte antigen (HLA) antibodies in HLA-mismatched haematopoietic cell transplant (HCT) is known, but the importance of HLA antibodies in HLA-matched HCT is unclear. We hypothesized that HLA antibodies detected before HCT would cause platelet transfusion refractoriness during HCT and investigated this in a multi-centre study. Pre-HCT samples from 45 paediatric patients with sickle cell disease (SCD) undergoing HLA-matched HCT were tested for HLA class I antibodies. The number of platelet transfusions received before day +45 was compared between those with and without antibodies. Thirteen of 45 (29%) patients had a positive HLA class I antibody screen, and these patients received significantly more platelet transfusions than patients without antibodies (median 19 vs. 7.5, P = 0.028). This platelet transfusion association remained significant when controlling for conditioning regimen. Among alloimmunized patients, there was no association between the panel-reactive antibody and the number of platelet transfusions. Patients with HLA class I antibodies also had a higher incidence of acute graft-versus-host disease (GVHD): 6/13 (46%) vs. 3/32 (9%), P = 0.011. Pre-HCT HLA class I alloimmunization is associated with increased platelet transfusion support and acute GVHD in paediatric HLA-matched HCT for SCD. Further studies are needed to investigate the pathobiology of this association.
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8.
Serum ferritin is not a reliable predictor to determine iron overload in thalassemia major patients post hematopoietic stem cell transplantation
Jarisch, A., Salzmann-Manrique, E., Cario, H., Grosse, R., Soerensen, J., Fischer, R., Schulz, A., Hammerstingl, R., Wunderlich, A., Bader, P.
European journal of haematology. 2018
Abstract
OBJECTIVE Iron overload (IO) in transfusion-dependent anemia persists after hematopoietic stem cell transplantation (HSCT) and can cause long-term organ damage. In many studies, the diagnosis of IO before and after HSCT is based on serum ferritin (SF) levels rather than on assessment of liver iron concentration (LIC) by MRI or SQUID. METHOD In a multicenter, retrospective study we analyzed the concordance for indication of iron depletion therapy and correlation between LIC and SF of 36 thalassemia patients after HSCT. LIC was determined either by MRI-R2 (Ferriscan((R)) ) or SQUID. RESULTS The concordance between LIC and SF varies over time after transplant (P=0.011). The correlation between SF and LIC was strong in the first year (Spearman's rho 0.75; P<0.001). In agreement, the concordance between SF and LIC concerning indication for treatment was close to 1 with an overall error rate ca. of 10%. Especially in the first year after HSCT, SF underestimates the degree of iron overload. However, in the longitudinal analysis since the second year post HSCT onwards no association was found between LIC and SF (P=0.217). Furthermore, in the second year after HSCT the overall error rate was 35% whereas in the 3(rd) , 4(th) and >4(th) year it was 58%, 60% and 25%, respectively. CONCLUSIONS Our data suggest serum ferritin is not a reliable predictor to determine iron overload in thalassemia patients after HSCT. This article is protected by copyright. All rights reserved.
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9.
One-year results from a prospective randomized trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation
Inati, A., Kahale, M., Sbeiti, N., Cappellini, M. D., Taher, A. T., Koussa, S., Nasr, T. A., Musallam, K. M., Abbas, H. A., Porter, J. B.
Pediatric Blood & Cancer. 2017;64(1):188-196
Abstract
BACKGROUND Iron overload is well documented in patients with beta-thalassemia major, and patients who have undergone hematopoietic stem cell transplantation (HSCT) remain at risk as a result of pre- and immediate post-HSCT transfusions. PROCEDURE This is a prospective, randomized, 1-year clinical trial that compares the efficacy and safety of the once-daily oral iron chelator deferasirox versus phlebotomy for the treatment of iron overload in children with beta-thalassemia major following HSCT. RESULTS Patients (aged 12.4 years) received deferasirox (n = 12, 10 mg/kg/day starting dose) or phlebotomy (n = 14, 6 ml/kg/2 weeks) for 1 year. In two and five patients, deferasirox dose was increased to 15 and 20 mg/kg/day, respectively. Magnetic resonance imaging (MRI)-assessed liver iron concentration (LIC) decreased with deferasirox (mean 12.5 +/- 10.1 to 8.5 +/- 9.3 mg Fe/g dry weight [dw]; P = 0.0005 vs. baseline) and phlebotomy (10.2 +/- 6.8 to 8.3 +/- 9.2 mg Fe/g dw; P = 0.05). LIC reductions were greater with deferasirox than with phlebotomy for patients with baseline serum ferritin 1,000 ng/ml or higher (-8.1 +/- 1.5 vs. -3.5 +/- 5.7 mg Fe/g dw; P = 0.048). Serum ferritin and non-transferrin-bound iron also decreased significantly. In two patients with severe cardiac siderosis, a clinically relevant improvement in myocardial T2* was seen, following phlebotomy and deferasirox therapy (n = 1 each). Adverse effects with deferasirox were skin rash, gastrointestinal upset, and increased liver function tests (all n = 1), while those for phlebotomy were difficulty with venous access (n = 4) and distress during procedure (n = 1). Parents of 13/14 children receiving phlebotomy wished to switch to deferasirox, with 1/14 being satisfied with phlebotomy. CONCLUSIONS Deferasirox treatment or phlebotomy reduces iron burden in pediatric patients with beta- thalassemia major post-HSCT, with a manageable safety profile. Copyright © 2016 Wiley Periodicals, Inc.