scholarly journals Impact of Iron Overload and Iron Removal Therapy on Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in the Patients with Severe Aplastic Anemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5741-5741
Author(s):  
Tianzhong Pan ◽  
Baolin Tang ◽  
Xiaoyu Zhu ◽  
Huilan Liu ◽  
Kaidi Song ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Iron Overload ◽  
Implantation Rate ◽  
Iron Removal ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract:The aim of this study was to evaluate the Impact of iron overload and iron removal therapy on the outcome of allogeneic hematopoietic stem cell transplantation (SCT) in patients with severe aplastic anemia (SAA). Forty-five transplant patients with SAA were retrospectively analyzed. Patients were divided into two groups according to whether there was iron overload or not: iron overload group (n=23) and non-iron overload group (n=22). The iron overload group had higher 1-year transplant-related mortality (TRM) (30.4% vs. 4.5%, P = 0.02), lower 1-year transfusion-free survival (TFS) (40.6% vs. 81.8%, P = 0.007) and lower 1-year overall survival (OS) (54.8% vs. 90.2%, P = 0.003) than the non-iron overload group. However, there was no significant difference in implantation rate, pre-engraftment syndrome (PES) and acute graft-versus-host disease (aGVHD, grade III-IV) between the two groups. Furthermore, the multivariate analysis revealed that iron overload was an independent risk factor affecting OS (HR = 36.88, P = 0.03). The patients in iron overload group were divided into two subgroups according to the time of iron removal using deferasirox 20mg/kg/d. Specifically, group A (n=17) was treated with deferasirox 20mg/kg/d for 3 months or less and group B (n=6) treated for more than 3 months. The results showed that group B had a lower one-year TRM (0% vs. 41.2% , P = 0.07), higher 1-year TFS (66.7% vs. 31.4%, P = 0.18) and higher 1-year OS (100% vs. 31.4% , P = 0.02) than group A. There were no significant difference in implantation rate, PES and aGVHD ( III-IV) between the two groups. In conclusion, the results indicate that iron overload before transplantation was associated with increased TRM and decreased OS, suggesting that iron overload was associated with worse transplantation outcomes. However, standardized iron removal therapy could reverse the adverse effects of iron overload on the outcomes of transplantation to a certain extent and improve the prognosis significantly. Disclosures No relevant conflicts of interest to declare.

Subclinical Alterations in Coagulation in Patients during Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5292-5292
Author(s):  
Qian Jiang ◽  
Xiao Jun Huang ◽  
Kaiyan Liu ◽  
Huan Chen ◽  
Yuhong Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
Group A ◽  
Group B ◽  
D Dimer

Abstract Objective To evaluate the alterations in coagulation in patients during modified busulfan plus cyclophosphamide (BUCY) ± antithymocyte globulin (ATG) before allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to assess the effect of ATG on coagulation system as part of conditioning regimen. Methods Thirty-five patients with various hematological malignancies undergoing allo-HSCT were assessed. Nineteen patients from HLA-identical siblings (group A) were conditioned with modified BUCY regimen, included cytarabine (2g/m2 i.v., day -9), busulfan (4mg/kg p.o. in divided doses daily, day -8 to day -6), cyclophosphamide (1.8g/m2 i.v., day -5 and day -4) and Me-CCNU (250mg/ m2 p.o., day -3). Sixteen patients from HLA-mismatched family members or HLA-matched unreleated donors (group B) were conditioned with modified BUCY + ATG regimen, added cytarabine (4g/m2 i.v., day -10 and -9) and rabbit ATG (2.5mg/kg i.v., day -5 to day -2, SangStat S.A.S., France). Blood samples were obtained before the start of regimen until day +1 after allo-HSCT. The following laboratory parameters were measured: prothrombin time (PT), active partial thromboplastin time (APTT), Fgrinogen (Fg), antithrombin (AT), D-Dimer, Fgrin degradation product (FDP), platelet (PLT), liver enzymes and bilirubin. VIII:C, IX:C, XI:C and XII:C in some blood samples with prolonged APTT were determined. Clinical hemorrhagic symptoms were monitored. Results From day -5 of conditioning regimens, temporary lengthening of APTT, which peaked on day -3, occurred in 16/19 (84.2%) patients in group A and 19/19 (100%) patients in group B, continued rise in Fg occurred in 17/19 (89.5%) patients in group A and 19/19 (100%) patients in group B, a progressive decrease of PLT was observed in all patients of two groups. Alterations of Fg and PLT were more significant in group B compared to those in group A. Transient D-Dimer increase was detected only in group B on day -3. Among intrinsic pathway coagulation factors, XII:C and XI:C were decreased commonly and significantly when APTT was prolonged. No difference between the two groups could be found with regard to PT, FDP, AT and liver parameters which remained nearly in normal ranges. Most of patients in two groups did not have overt bleeding manifestations. Conclusions Modified BUCY ± ATG conditioning regimen can induce subclinical alterations in coagulation. The regimen contained ATG has more significant effect on coagulation parameters.

The Impact of Sex Steroids Inhibiter on Thymic Function Following Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4599-4599
Author(s):  
Xiaodan Luo ◽  
Qifa Liu ◽  
Zhiping Fan ◽  
Yu Zhang ◽  
Juan Ning
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Thymic Function ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
The Impact

Abstract Objective To evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT). Methods Established model of allogenic murine HSCT (C57BL/6→BALB/c). The severity of acute graft-versus-host-disease (GVHD) was assessed by a clinical scoring system that incorporates five clinical parameters: weight loss, posture, activity, fur texture and skin integrity. The intra-cellular levels of interferon-γ (INFγ), tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) in thymocyte were analyzed by protein array and thymic function was evaluated by quantification of signaljoint TCR rearrangement excision circles (sjTRECs). Results Recipients in group A (allogenic mice), B( allogenic LHRH castrated-mice) and C (syngenic mice) all attained hematopoiesis reconstitution. White blood cell counts of mice in groups A, B and C were over 1.0×109/L on day (10.60±1.34), day (9.40±0.55) and day (9.40±0.89), respectively. There was no significant difference among the time of hematopoiesis reconstitution in three groups. The time of acute GVHD occuring was on day +11±0.5 and +14±0.5 posttransplantation, respectively, in groups A and B, and all mice had acute GVHD with the incidence of 100% in groups A and B. The average scores of acute GVHD in groups A and B were (1.56±0.51) and (0.92±0.49), respectively. Acute GVHD scores in group A was significantly higher than that in group B (P=0.000). The levels of INFγ, TNFα and IL-1β in control groups were 1.67±1.76 ng/ml, 1.69±1.07 pg/ml and 5.55±3.56 pg/ml, respectively. The levels of INFγ in groups A, B and C were (10.74±2.55) ng/ml,(6.81±2.33) ng/ml and (5.52±3.96) ng/ml, respectively. The levels of TNFα were (7.51±2.89) pg/ml, (4.30±0.63) pg/ml and (3.36±2.31) pg/ml, respectively. The levels of IL-1β were (25.83±8.91) pg/ml, (19.33±3.03) pg/ml and (11.94±4.00) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P=0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those of control group (P 0.010,0.037,0.000). The levels of INFγ in group C were significantly higher than those of the control group (P=0.044). Among groups A, B and C, there were significant differences in the levels of INFγ, TNFα and IL-1β (P=0.001,0.000,0.000). The levels of INFγ and TNFα in group A were significantly higher than those in group B (P=0.041,0.013). The levels of INFγ, TNFα and IL-1β in group A were significantly higher than those in group C (P=0.009, 0.002, 0.000). The analysis of linear regression showed that the average levels of INFγ paralled with aGVHD scores (r2 0.363,P=0.038). The average sjTRECs copies/1000 PBMNCs were (39.41±44.68) in the control group and (12.29±13.02), (58.01±71.82) and (19.61±14.59) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P=0.575). Conclusion INFγ ATNFα and IL-1β might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intracellular levels of INFγ and TNFα in thymocyte.

scholarly journals Inefficacy of Immunosuppressive Therapy for Severe Aplastic Anemia Progressing From Non-SAA: Improved Outcome After Allogeneic Hematopoietic Stem Cell Transplantation

2021 ◽  
Vol 11 ◽  
Author(s):  
Limin Liu ◽  
Xin Zhao ◽  
Miao Miao ◽  
Yanming Zhang ◽  
Wenjing Jiao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Group A ◽  
Group B

Background and AimsThis study aimed at comparing the efficacy and safety of severe aplastic anemia (SAA) cases that had met the criteria for SAA at the time of diagnosis (group A) with SAA that had progressed from non-SAA (NSAA) (group B), both undergoing first-line immunosuppressive therapy (IST). Additionally, group B was compared with SAA that had progressed from NSAA and who had been treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) (group C).MethodsWe retrospectively compared 608 consecutive patients in group A (n = 232), group B (n = 229) and group C (n = 147) between June 2002 and December 2019. Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values, treatment-related mortality (TRM), secondary clonal disease, 5-year overall survival (OS) and failure-free survival (FFS) were indirectly compared between group A and group B, group B and group C.ResultsSix months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values in group A was higher than in group B (65.24% vs. 40.54%, P < 0.0001; 23.33% vs. 2.25%, P < 0.0001); the same was true for group C (92.50% vs. 2.25%, P < 0.0001). The rate of relapse in group B was higher than in group C (P < 0.0001), but there were no differences in TRM and secondary clonal disease (P > 0.05). There were no differences in estimated 5-year OS between groups A and B (83.8% ± 2.6% vs. 85.8% ± 2.6%, P = 0.837), or between B and C (85.8% ± 2.6% vs. 77.9% ± 3.4%, P = 0.051). The estimated 5-year FFS in groups A and C was higher than for group B (57.1% ± 3.3% vs. 39.7% ± 3.4%, P < 0.001; 76.7% ± 3.5% vs. 39.7% ± 3.4%, P < 0.0001).ConclusionThese results indicate that IST is less effective in SAA progressing from non-SAA but allo-HSCT can improve outcomes.

STI 571 Combined with Hematopoetic Stem Cells Transplantation for Chronic Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4854-4854
Author(s):  
Fan Yi Meng ◽  
Jing Sun ◽  
Qifa Liu ◽  
Dan Xu ◽  
Yongqiang Wei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Phase ◽  
Hematopoietic Stem ◽  
Sti 571 ◽  
Group A ◽  
Group B

Abstract Objective: to study the efficacy of STI 571 combined with allogenic hematopoietic stem cell transplantation (Allo-HSCT) or autologous peripheral blood stem cell transplantation (APBSCT) in chronic myeloid leukaemia (CML). Methods: 18 CML patients were divided into 2 groups: group A (14) and group B (4). Patients in group A including 10 in CML accelerating phase or blast crisis phase, 4 in chronic phase. They all underwent Allo-HSCT and the median duration of STI 571 treatment before Allo-HSCT was 25 days (7–60d). 9 had related complete HLA-matched donors and 5 had unrelated complete matched donors, the preparation regimen was TBI+CTX +VP16 or BU/CY ±ATG, routine protocol was used to prevent graft versus host disease (GVHD). Patients of group B were all in chronic phase, the median duration of STI 571 treatment before APBSCT was 5.5 months (4–26d), and bcr/abl detected by FISH was continuously negative. Mobilization protocol was CAE + G-CSF, 3 of 4 underwent TBI+ CY+ VP16 followed by APBSCT. Results: in group B, PBSC were separated after 5 days of mobilization, and (3.9–9.6)×106/kg Cd34+ cells were obtained, however FISH- bcr/abl positive cells in separation products were higher than in bone marrow cells before separation (0.8% vs 2.8%). After a median follow up of 24 months (18–28 months), 2 cases relapsed, and one remains FISH-bcr/abl negative. In group A, 8 had GVHD, and after a median follow up of 8 months (4–20 months), 2 cases relapsed, 2 died of transplantation- related complications, 1 died of relapse, 9 remained disease free. Hematopoiesis was reconstituted in 8–21 days in patients of group A. Conclusions: no obvious side effect was observed in STI 571 combined hematopoietic stem cell transplantation in CML patients.

The Efficacy and Safety of Recombinant Human Thrombopoietin in Patients with Hematological Malgnancies After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4565-4565
Author(s):  
Miao Miao ◽  
Wu Depei ◽  
Aining Sun ◽  
Ying Wang ◽  
Lingzhi Yan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Platelet Transfusion ◽  
Severe Thrombocytopenia ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Recombinant Human Thrombopoietin

Abstract Abstract 4565 OBJECTIVE: To evaluate the efficacy and sefety of recombinant human thrombopoietin(rhTPO) prior to engraftment in adults with hematological malignancie who received allogeneic haematopoietil stem cell transplantation(Allo-HSCT). METHODS: This sutdy was a randomized, controlled clinical trial,38 patients were hematological malignancie, inclulding acute and chrinic myeloid leukemia, acute lymphoblastic leukemia, lymphoma.They received Allo-HSCT and were randomly divided into groups(group A 19 cases, group B 19 cases).The group A was no-rhTPO as control, the group B were received rhTPO 15000U/d from +1 day, and continued until the untransfused platelet count was >70×109/L for two consecutived days. Patients received platelete transfusion when they developed severe thrombocytopenia<20×109/L. Efficacy and sefety of rhTPO on the outcome of Allo-HSCT were evaluated. RESULTS: In both group A and B, platelet decrease after Allo-HSCT had no sognificant difference. The platelet engraftment duration of group A and B was 15.68±1.36(range 11–31) days and 13.47±0.72(range 9–21) days, respectively. The amount of platelet transfusion of group A and B was 4±0.55(range 20–130) units and 2.89±0.36(range 0–50) units, respectively. The effects of rhTPO on neutrophil engraftment, hepatic function, renal function, alloergic reations and acute GVHD were not found. CONCLUSION: The platelet engraftment duration of group B was shorter than that of group A(t=27.2, p<0.001), the amount of need platelet transfusion was significently less than those in the group A.There was a statistically significant difference in platelet engraftment and platelet transfusion needed(t=2.523, p<0.05). Administration of rhTPO prior to platelet engraftment after Allo-HSCT seem to be efficacy and safe. Disclosures: No relevant conflicts of interest to declare.

Relapse of Myelodysplastic Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation as Blood Bank Sees It: a Case Report

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S157-S158
Author(s):  
C E Kanakis ◽  
K Gvozdjan
Keyword(s):  
Stem Cell ◽  
Case Report ◽  
Immune System ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Blood Bank ◽  
Disease Relapse ◽  
Hematopoietic Stem ◽  
Group B

Abstract Introduction/Objective Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for patients with myelodysplastic syndrome (MDS). Nonetheless, a large proportion of patients with MDS experience disease relapse. Declining donor chimerism and detection of recurrent gene mutations have been used as indicators of graft failure and recurrent disease. Blood Bank serologic findings have rarely been described as first indicators of disease relapse in this setting and could potentialy add to engraftment and relapse surveillance testing. Methods/Case Report A 72-year-old, ABO group O, RhD positive male with history of anti-Fyb alloimmunization underwent allo-HSCT from an ABO group B, RhD negative, Fyb positive donor as part of the treatment for MDS. Successful engraftment was achieved, and the patient’s red blood cell phenotype transitioned to ABO group B, RhD negative, Fyb positive. Two years following allo-HSCT, the patient received chemotherapy for recurrent cholangiocarcinoma. Supportive blood component transfusions were provided, all of which typed as RhD negative. However, new antibody with anti-D specificity was detected in serum while the patient still typed as ABO group B, RhD negative, preceding anti-D and later recurrent anti-Fyb detection in eluate, and prompting further chimerism testing. Declining donor chimerism was noted (72% donor, compared to &gt;98% donor on prior chimerism testing). Chemotherapy and donor-lymphocyte infusion were initiated. Results (if a Case Study enter NA) NA Conclusion The early detection of de novowlvw anti-D was most consistent with resurgence of patient’s erythroids within the bone marrow in the presence of donor’s immune system. This was followed by sufficient peripheralization of patient’s red blood cells and detection of anti-D in the eluate. Lastly, the switch to recipient’s immune system is evidenced by recurrent detection of anti-Fyb in the eluate. This case, therefore, emphasizes the utility of Blood Bank serology in raising suspicion for disease relapse and guiding further allo-HSCT patient management. More systematic use of Blood Bank serology may serve as a time- and cost-effective adjunct to the current strategies employed for detection of disease recurrence in allo-HSCT recipients.

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