scholarly journals Assessment of Iron Overload in Pediatric Patients With Thalassemia Major During One Year Follow-Up After Hematopoietic Stem Cell Transplantation Using T2 ∗ MRI Technique

2013 ◽  
Vol 19 (2) ◽  
pp. S248
Author(s):  
Amir Ali Hamidieh ◽  
Sirous Tayebi ◽  
Maryam Behfar ◽  
Ahmadreza Shamshiri ◽  
Kamran Alimoghaddam ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Pediatric Patients ◽  
Thalassemia Major ◽  
Hematopoietic Stem ◽  
One Year ◽  
T2 Mri

scholarly journals Lipid Complications after Hematopoietic Stem Cell Transplantation (HSCT) in Pediatric Patients

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2500
Author(s):  
Gabriela Bis ◽  
Wojciech Szlasa ◽  
Katarzyna Sondaj ◽  
Iga Zendran ◽  
Monika Mielcarek-Siedziuk ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Pediatric Patients ◽  
Function Analysis ◽  
Density Lipoprotein ◽  
Hematopoietic Stem

HSCT (hematopoietic stem cell transplantation) is a widely applied method of treatment of pediatric patients with leukemia and other bone marrow-associated disorders. Metabolic disturbances can appear as procedure side effects. This study aimed to report incidence of lipid and thyroid disorders and time of their onset in pediatric patients after HSCT. There were 198 pediatric patients (123 males) aged 0.5–20 years who were subjected to HSCT. Patients were mostly diagnosed with Acute Leukemia (n = 190). The analysis of lipids, thyroid hormones, and thyroid antibodies levels comprised one month before the HSCT to last follow up visit between 2016 and 2019 (median 3.8 ± 1.8 years after HSCT). In males, the triglycerides levels increased over two times in the course of HSCT in both patients with initially low and elevated HDL (high-density lipoprotein) levels. Most of the lipid disorders occurred in six months after HSCT. Patients treated with L-thyroxine exhibited decreased LDL (low-density lipoprotein) levels. HDL remained at a lower level in males. Thyroid hormone abnormalities were evenly distributed in time until 4 years after HSCT. Patients require long term follow up including lipid metabolism and thyroid function analysis. HSCT survivors demand introduction of polyunsaturated fatty acids into the diet to reduce risk of developing the lipid complications.

scholarly journals Allogeneic-Hematopoietic Stem Cell Transplantation Is Effective and Safe for Relapsed/ Refractory B-ALL Patients Who Cannot Get Remission or MRD Negative after CART Treatment

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1843-1843
Author(s):  
Yanzhi Song ◽  
Zhihui Li ◽  
Yongqiang Zhao ◽  
Fan Yang ◽  
Erhui Yuan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Tp53 Mutation ◽  
Fusion Gene ◽  
Hemorrhagic Cystitis ◽  
Hematopoietic Stem ◽  
One Year ◽  
Grade Iii

Abstract Background: Chimeric antigen receptor T-cell (CART) Therapy has induced high rates of complete remission (CR) in the patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), but a small portion of them still cannot obtain CR or minimal residual disease (MRD) negative. Salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be the only curative treatment for this setting. According to previous reports, around 20% to 30% overall survival (OS) has been seen in the patients with r/r B-ALL treated with salvaged allo-HSCT. Aim: In current study, the efficacy and safety of allo-HSCT for the patients with r/r B-ALL who cannot achieve CR or MRD negative after CART therapy were evaluated. Methods: Between January 2018 and June 2021, 23 consecutive patients with r/r B-ALL who did not achieve CR or MRD negative after CART treatment and received allo-HSCT in our hospital were included. The median age was 10 (1-47) years old. The median disease course was 24 (8-89) months. Eight patients were in non-remission (NR) and 15 cases were MRD positive (10 detected by flow cytometry, and 5 detected by RT-PCR). The median blast in bone marrow (BM) in NR series was 39 (0.5-94)% in which two patients were only extramedullary leukemia, and the median flow cytometric MRD level in BM in MRD positive series was 0.11 (0-3)%. One patient had TP53 mutation, one had MLL-AF4 fusion gene and one had both TP53 mutation and MLL-AF4 fusion gene. Nineteen patients (82.6%) received at least two kinds of CART therapies (murinized CD19, humanized CD22, humanized CD19) and 4 patients (17.4%) received one kind of CART therapy (murinized CD19, humanized CD22 or humanized CD19). Three patents underwent second transplantation. Eighteen patients (78.3%) received allo-HSCT from haploidentical donors and 5 patients (21.7%) from unrelated donors (HLA 10/10 matched in 3 and 9/10 matched in 2). Myeloablative conditioning regimens with total body irradiation (fractionated, total 10 Gy) /etoposide (200mg/m 2 x 3) /fludarabine (30mg/m 2 x 5) or cyclophosphamide (1.8g/m 2 x 2) /rabbit anti-T-cell globulin were used. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis. Some patients received maintenance regimens with targeted medicine based on their fusion genes or gene mutations up to 2 years post-transplant. Results:All patients achieved durable engraftment. For the patients in NR (n=8) before transplantation, the median follow-up time was 336 (22-803) days. Four of them had been alive free of leukemia and MRD negative, and 4 patients died of relapse. One-year OS and leukemia-free survival (LFS) were 85.7% and 35.7%, respectively. No patient died of transplant-related events. Two patients developed grade III acute GVHD (aGVHD) and 1 patient had extensive chronic GVHD (cGVHD). All of them were resolved with immune-suppressants. CMV and EBV reactivation was detected in 6 and 1 patients, respectively. One patient had severe lung fungal infection and 1 case developed mild hemorrhagic cystitis. For the patients with MRD positive (n=15) before transplantation, the median follow-up time was 359 (42-872) days and one-year OS and LFS were 68.1% and 40.9%, respectively. Seven patients relapsed, three of them achieved MRD negative CR with donor-derived CART therapies, and 3 patients died of relapse. Six patients developed grade III~IV aGVHD and one patient had extensive cGVHD. All of them were resolved except one patient died from grade IV aGVHD. CMV and EBV reactivation was found in 6 and 1 patients, respectively. Three patients had mild hemorrhagic cystitis. No other severe infection occurred. C onclusion: Our results indicate that salvaged allo-HSCT has improved survival remarkably in r/r B-ALL patients who failed not only chemotherapy but also CART therapy.One-year OS and LFS can reach 85.7% and 35.7%, 68.1% and 40.9% in NR and MRD positive cohorts, respectively. Transplant-related mortality is quite low (1/23). The leading cause of death is disease recurrence (7/23). Under our protocol, allo-HSCT is a safe and effective salvaged modality for r/r B-ALL who cannot obtain CR or MRD negative with CART therapy. Disclosures No relevant conflicts of interest to declare.

Interim Results from a Phase 2, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with Beta-Thalassemia Major

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 959-959
Author(s):  
M Akif Yesilipek ◽  
Gulsun Karasu ◽  
Zuhre Kaya ◽  
Baris B Kuskonmaz ◽  
Vedat Uygun ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Cell Transplantation ◽  
Study Drug ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Phase 2 ◽  
Hematopoietic Stem

Abstract Introduction: Hematopoietic stem cell transplantation (HSCT) is being increasingly used as curative therapy for severe disorders of the hematopoietic system and transfusional iron overload (TIO) contributes considerably to treatment-related morbidity and mortality after HSCT. Management of iron overload in the post-HSCT setting may be complicated since the use of therapeutic phlebotomies is often not feasible due to ongoing anemia and compliance to deferoxamine is low. Studies that evaluate the safety dose of deferasirox (DFX), which is the most commonly used chelation therapy, in this setting are limited. Purpose & Methods: This is a prospective, phase 2, multicenter, single-arm study to evaluate the efficacy and safety of iron chelation with oral DFX in beta-thalassemia major (TM) patients who have undergone HSCT. The study was conducted in 7 centers from Turkey. The primary objective was to evaluate if DFX could provide clinically safe chelation in a target pool of 26 pediatric patients with TIO within a minimum of 6 months and maximum of 2 years after related/unrelated HSCT. Patients had to be transfusion-independent and have iron overload at screening defined by serum ferritin (SF) of >1000 μg/L or cardiac MRI T2* <20 ms or liver iron concentration (LIC, by MRI R2) of ≥5 mg/g. The study included male and female TM patients ≥2 to <18 years old who had undergone HSCT with a washout period from immunosuppressive therapy of at least 3 months. Patients received DFX at an initial dose of 10 mg/kg/day with up titration every 3 months by 5 mg/kg/day per investigator judgment to a maximum of 20 mg/kg/day. Therapy continued for 52 weeks or until SF reached below 500 μg/L. Aside from AE monitoring, assessments were undertaken at baseline and every 28 days (unless closer assessments were need for dose initiation and adjustment) and included complete blood counts, biochemistry and urinalysis, and SF. MRI assessment of liver (R2) and cardiac (T2*) iron were also conducted at baseline and 52 weeks. Results: Interim data from the first 18 of 26 patients (mean age 8.3 years, 66.7% males) who completed 12 months follow up are presented in this analysis. A total of 97 AEs were recorded in the 18 patients. The majority of AEs were of Grade I (n=57) or II (n=34) severity. Five (5.2%) were suspected to be related to study drug and 6 AEs (6.2%) were considered serious. Five (5.2%) AEs resulted in study drug temporary interruption or dose adjustment, 2 (2.1%) required hospitalization, 54 (55.7%) required concomitant medication, while 36 (37.1%) had no action taken. Three patients had dose decrease due to AEs. The dose was re-escalated up to 20 mg/kg/day after the AEs resolved. In total, 11 (61.1%) patients achieved 20 mg/kg/day. Only one patient dropped out due to progressive ALT increase. Median ALT level decreased from 26 IU/L (range: 10-117) at baseline to 18 IU/L (range: 9-101) at week 52. The median SCr was similar at baseline 0.4 mg/dL (range: 0.2-0.6) and week 52 0.4 mg/dL (range: 0.2-0.8). Median cystatin C was similar at baseline 0.7 mg/mL (range: 0.6-0.9) and week 52 0.7 mg/mL (range: 0.5-1.1) (Figure 1A-B). Five patients had proteinuria at baseline and increased proteinuria compared to previous visit by dipstick analysis was described in 7 (38.9%) patients, irrespective of DFX dose by 52 weeks. No patient with proteinuria required any dose adjustments by 52 weeks. SF significantly and consistently decreased throughout the 52 weeks from a median of 1752.3 μg/L (range: 873.7-2716) to 915.2 μg/L (range: 250.1-2740), p<0.001 (Figure 2). At week 52, 6 (33.3%) patients had reached SF <500 μg/L. LIC also significantly decreased from a median of 9.9 mg/g (range: 4.8-43) to 4.1 mg/g (range 0.9-8.5), p<0.001. Cardiac T2* increased from a median of 26.1 ms (range: 18.7-41) to 28.8 ms (18.5-44), p=0.605. Conclusions: Our preliminary results showed that DFX up to 20 mg/kg/day is safe and effective in reducing iron burden for TM patients following HSCT. This was evident through significant reductions of systemic, hepatic and cardiac iron overload. Final data from the completed study should confirm these findings and establish the role for DFX in this patient population. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Dag: Novartis: Employment. Birkent:Novartis: Employment.

Allogeneic Halpo-Identical Hematopoietic Stem Cell Transplantation for High-Risk Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5514-5514
Author(s):  
Jing Bo Wang ◽  
Xin Hong Fei ◽  
Yu Ming Yin ◽  
Hao Yu Cheng ◽  
Wei Jie Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
One Year ◽  
The One

Abstract Objective To retrospectively evaluate the results of allogeneic halpo-identical hematopoietic stem cell transplantation for high-risk leukemia. Methods From June 2012 to January 2015, total 60 patients with high-risk leukemia were enrolled, including 18 cases of ALL, 37cases of AML and 5 case of CML-BP. Including criterions: 1) ≥CR1; 2) relapse within 6 months after remisson. The average leukemia burden was 53% in bone marrow. All patients received HLA haplo-identical stem cells transplantation from parent or sibling donors. Myeloablative conditioning regimens consist of 7cases of BuCy, 26 cases of TBI/FLAG, 15 cases of TBI/Cy, and 12 cases of FLAG that followed by reduced-intensified BUCY. All patients received cyclosporine A, MMF and methotrexate for GVHD prophylaxis. Analyzed outcomes were hematological engraftment, incidence of acute and chronic GVHD, incidence of relapse, and nonrelapse mortality (NRM), Overall survival (OS) and Disease-free survival (DFS). Results The median mononuclear cells and CD34+ for transfusion were 9.08(7.02-24.4)*108/Kg and 3.42(0.8-12.1)*106/Kg. All 60 patients achieved stable engraftment. The median time of ANC≥0.5*10^9/L was 16 (8-23) days. And for platelet ≥20*10^9/L, the median was 22 (8-150) days. 38 patients developed acute GVHD, the accumulative incidence of aGVHD was 66.4%, the accumulative incidence of II-IV grade aGVHD was 35%, and the accumulative incidence of III-IV grade aGVHD was 15%. 26 patients developed cGVHD (12 patients extensive, 14 patients limited), the accumulative incidence of cGVHD was 88.2% and for extensive type, the accumulative incidence was 67.4%. The accumulative incidence of CMV infection was 54.1%, and the accumulative incidence of EBV infection was 16.3%. 10 patients developed virus cystitis. The number of Bacterial and fungal infected patients were 51 and 27, respectively. The median follow-up time post transplantation was 11(1-36) months, 14 patients relapsed and the accumulative incidence of relapse was 27%. For AML, ALL and CML-BP patients, the accumulative incidence of relapse were 26.6%, 34.8% and 0%, respectively. The median follow-up time post transplantation was 11months, 21 patients died and the main causes were relapse (11 cases), infection (5 cases), cGVHD (2 cases) and diffuse alveolar hemorrhage (3 cases). Among 60 patients, 39 patients survived. The one-year and two-year accumulative incidences of OS were 61.8% and 49.5%, respectively. The one-year and two-year accumulative incidences of DFS were 53.8% and 47.8%, respectively. For AML, ALL and CML-BP patients, the two-year accumulative incidence were 52.6%, 34.4% and 66.7%, respectively. The non-relapse mortality was 10. The one-year and two-year accumulative incidences of NRM were 19.4% and 28.4%, respectively. Conclusion Our clinical results have shown that the salvaged HSCT is a promising modality for treatment of high-risk AL with high leukemia burden. Disclosures No relevant conflicts of interest to declare.

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