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| ID | Type | Description | Link |
|---|---|---|---|
| Peking University | Registry Identifier | Peking University |
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Myelofibrosis (MF) is a myeloproliferative neoplasm causing bone marrow failure and high risk of leukemia transformation. JAK2 inhibitors improve symptoms but do not cure MF. Allogeneic stem cell transplantation (allo-HSCT) is the only potential cure, though limited donor availability restricts access. Haploidentical transplantation shows promise but associated with higher graft failure and treatment related mortality. We recently developed a novel regimen of haplo-SCT for MF. This study aims to investigate this novel protocol in a prospective trial to improve MF outcomes.
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells, reactive hyperplasia of bone marrow stromal cells, and secondary inflammation and fibrosis, leading to progressive bone marrow failure and a high risk of acute myeloid leukemia transformation, with a median survival of about 6 years. While JAK2 inhibitors like ruxolitinib have been approved to improve symptoms and survival in MF patients, they do not provide a cure. Allogeneic stem cell transplantation (allo-HSCT) remains the only potential cure, but limited availability of matched sibling and unrelated donors often prevents patients from receiving this treatment. Haploidentical stem cell transplantation has shown good efficacy in leukemia but is less studied in MF, possibly due to concerns about graft failure, complications, and high transplant-related mortality. Our team has applied a novel haploidentical transplantation protocol for treating MF, which has shown promising results in preliminary observations. This study aims to further validate the effectiveness of this protocol through a prospective clinical trial, potentially establishing an effective approach for HSCT in MF and improving overall transplant outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Haplo-SCT group | Experimental | Patients in this group will undergo haploidentical hematopoietic stem cell transplantation for the treatment of myelofibrosis. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Haploidentical hematopoietic stem cell transplantation | Procedure | This is a single-arm study in which all patients will undergo haploidentical hematopoietic stem cell transplantation for the treatment of myelofibrosis. Pre-transplant Evaluation: Evaluation includes status of primary Disease, donor specific antibodies (DSA), organ function (assessments for heart, liver, lungs, kidneys, and the nervous system), and Spleen size. Transplantation Protocol: Conditioning Regimen: Dac/TT/Bu/Flu/ATG regimen: Decitabine 100 mg/m², on day -12. Thiotepa (TT) 5 mg/kg/day, on days -11 and -10. Busulfan 0.8 mg/kg body weight, every 6 hours, on days -8 to -6. Fludarabine 30 mg/m², once daily, on days -6 to -2. Anti-thymocyte globulin (ATG) 2.5 mg/kg body weight, once daily, on days -5 to -2. Transplant Donor: Haploidentical donor. GVHD (Graft-versus-Host Disease) Prophylaxis Regimen: Cyclosporine, mycophenolate mofetil, and short-course methotrexate for GVHD prevention. Graft: Target MNC (Mononuclear Cells): 6-8 × 10⁸/kg. Target CD34+ stem cells: 5 × 10⁶/kg |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative incidence of Good graft function at day 60 | The cumulative incidence of achieving both neutrophil engraftment and platelet engraftment at day 60 after Hematopoietic stem cell transplantation, independent of transfusion and granulocyte growth factor support, using competing risk model. | Assessment at 60 days post-transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| Transplant-related mortality | TRM is defined as death due to any transplantation-related cause other than disease relapse. Transplant-related mortality will be calculated using a competing risks model. | From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment. |
| overall survival |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sun Yuqian | Contact | 861088326666 | sunyuqian83@hotmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University People's Hospital | Recruiting | Beijing | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36493799 | Result | Polverelli N, Hernandez-Boluda JC, Czerw T, Barbui T, D'Adda M, Deeg HJ, Ditschkowski M, Harrison C, Kroger NM, Mesa R, Passamonti F, Palandri F, Pemmaraju N, Popat U, Rondelli D, Vannucchi AM, Verstovsek S, Robin M, Colecchia A, Grazioli L, Damiani E, Russo D, Brady J, Patch D, Blamek S, Damaj GL, Hayden P, McLornan DP, Yakoub-Agha I. Splenomegaly in patients with primary or secondary myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT. Lancet Haematol. 2023 Jan;10(1):e59-e70. doi: 10.1016/S2352-3026(22)00330-1. Epub 2022 Dec 6. | |
| 22826273 |
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| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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The time from hematopoietic stem cell transplantation to death from any cause in patients with myelofibrosis. Overall survival will be calculated using the Kaplan-Meier method. |
| From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment. |
| Cumulative Incidence of Relapse | Relapse was defined as disease recurrence. The criteria for relapse include:
| From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment. |
| Incidence of GVHD | The incidence refers to the rate at which new cases of GVHD occur within a timeframe. Acute GVHD was classified as symptom presentation before 100 days after alloHCT and chronic GVHD was classified as symptom presentation >100 days after alloHCT. Each organ (skin, liver, and gut) was staged 1 through 4 for Acute (a) GVHD according to modified criteria based on the schema of the Mount Sinai Acute GVHD International Consortium (MAGIC), and patients were also assigned a grade of acute GVHD (I through IV) based on overall severity. Chronic (c) GVHD was graded in accordance with the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease Consensus Criteria. | From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment. |
| Disease-free survival | The time from hematopoietic stem cell transplantation to the first occurrence of disease relapse, progression, or death from any cause in patients with myelofibrosis. | From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment. |
| Neutrophil Engraftment | The time to neutrophil engraftment was defined as the first of three consecutive days with an ANC > 0.5 × 109/L. | From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment. |
| Platelet Engraftment | The time to platelet engraftment was defined as the first of seven consecutive days with a platelet count >20 × 109/L without transfusion support. | From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment. |
| Graft failure | Primary GF is defined by an ANC<0.5×109/l by day +28 following stem cell infusion, Hb <80 g/L and platelets <20×109 /L.Secondary GF is currently defined by EBMT criteria as the presence of an ANC<0.5×109/L occurring after initial engraftment and not related to relapse, infection or drug toxicity. | From baseline assessment at enrollment to the follow-up assessment at 28 days post-treatment. |
| Toxicity of conditioning | Toxicity of conditioning within 30 days of Hematopoietic Stem Cell Transplantation (HSCT) can be graded according to Common Terminology Criteria for Adverse Events (CTCAE):
| From baseline assessment at enrollment to the follow-up assessment at 30 days post-treatment. |
| Grade of Bone Fibrosis | The degree of bone marrow fibrosis as assessed by histopathological examination, categorized according to The European Consensus on grading of bone marrow fibrosis in patients with myelofibrosis after hematopoietic stem cell transplantation. | From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment. |
| Spleen Response | The change in spleen size, typically measured by imaging (e.g., ultrasound, CT scan), after hematopoietic stem cell transplantation, categorized as complete response, partial response, or no response according to the response criteria of IWG-MRT and ELN:
| From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment. |
| Result |
| Cervantes F, Dupriez B, Passamonti F, Vannucchi AM, Morra E, Reilly JT, Demory JL, Rumi E, Guglielmelli P, Roncoroni E, Tefferi A, Pereira A. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol. 2012 Aug 20;30(24):2981-7. doi: 10.1200/JCO.2012.42.0240. Epub 2012 Jul 23. |
| 32196650 | Result | Gangat N, Tefferi A. Myelofibrosis biology and contemporary management. Br J Haematol. 2020 Oct;191(2):152-170. doi: 10.1111/bjh.16576. Epub 2020 Mar 20. |