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

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.

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Pre-Transplant Test Dose vs. PK Studies during Conditioning Regimen To Target iv Busulfan in Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v110.11.3006.3006 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3006-3006

Author(s):

Sandeep Chunduri ◽

Rakesh Beri ◽

Lisa C. Dobogai ◽

Elizabeth Hurter ◽

Christina Mactal-Haaf ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Conditioning Regimen ◽

Test Dose ◽

Hematopoietic Stem ◽

Blood Samples ◽

The Mean

Abstract In this study we tested the efficacy of a test dose of iv busulfan in targeting blood levels of this drug during the conditioning regimen prior to an allogeneic hematopoietic stem cell transplant. We analyzed blood samples of 22 patients undergoing allogeneic hematopoietic stem cell transplantation with a busulfan-based conditioning regimen. Patients received a test dose of busulfan at 0.8 mg/kg as a 60 minute intravenous infusion. Serial blood samples were drawn at eight time points: 15 minutes before dose, at end of infusion, 15 minutes after completion, 30 minutes after completion, 60 minutes after completion, 2 hours after completion, 4 hours after completion, and 6 hours after completion. Pharmacokinetics (PK) studies were then performed at the Seattle Cancer Care pharmacokinetics laboratory. The AUC was determined using WinNonlin Professional software. The conditioning dose of busulfan was calculated by multiplying the test dose in mg/AUC × 4800. After the first dose of busulfan was administered, the same protocol was used to test busulfan PK. If the Busulfan AUC was therapeutic (between 4800 μM*min and 5200 μM*min) then the same dose was continued. If the Busulfan AUC was low or high then the third and fourth doses of busulfan were adjusted. The test dose of 0.8 mg/kg intravenous did not have any hematological side effects. The mean historic dose (solely based on weight) was 3.2 ± 0.1 mg/kg and the mean dose based on the test dose was 3.5 ± 0.5 mg/kg (p=0.02). In 12 patients where we also analyzed PK after the first day of conditioning regimen, AUC values of busulfan obtained during test dose and after day 1 dose were not different (p=0.7). The mean dose of busulfan based on test dose was 3.5 ± 0.6 mg/kg while the final dose based on day 1 busulfan PK was 3.6 ± 0.7 mg/kg (p=0.9). Nevertheless, in 2 CML patients who were on treatment with dasatinib or nilotinib at the time of the test dose, a higher AUC was observed (AUC 6065 and 6200, respectively). A pre-transplant busulfan test dose can be safely performed anytime prior to transplant and allows targeting the dose of busulfan efficiently, thus avoiding the requirement of PK studies during the conditioning regimen.

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

Frontiers in Oncology ◽

10.3389/fonc.2021.739561 ◽

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.

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

Blood ◽

10.1182/blood.v106.11.4854.4854 ◽

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.

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