Modified Post-Transplant Cyclophosphamide Regimen for Children With Juvenile Myelomonocytic Leukemia

Study Overview
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Brief Summary
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Hematopoietic stem cell transplantation (HSCT) is the only curative option for most of juvenile myelomonocytic leukemia (JMML). However, relapse after HSCT severely influence the long-term overall survival (OS). Researches demonstrate that these malignant myeloid disorders is a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents decitabine. However, hypomethylating therapy does not eradicate the malignant clone in JMML and an emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT. Graft-versus-host disease (GVHD) is major complication after HSCT as a threshold of the quality of patient life. Many data indicate that post -transplant cyclophosphamide (PT/Cy) is an effective method to control the occurrence of GVHD.

Detailed Description
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Hematopoietic stem cell transplantation (HSCT) is the only curative option for most of juvenile myelomonocytic leukemia (JMML). However, persistent disease statute and relapse after HSCT severely influence the long-term overall survival (OS). Researches demonstrate that JMML is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine. However, hypomethylating therapy does not eradicate the malignant clone in JMML and an emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT. Graft-versus-host disease (GVHD) is severe complication after HSCT. Post -transplant cyclophosphamide (PT/Cy) is an effective method to control the occurrence of GVHD. Based on these encouraging results, investigators launched a noval method for patients diagnosed as JMML and treated in our institution. They modified PT/Cy conditioning regimens. Patients all subsequently received modified DCAG regimen as the induction chemotherapy including decitabine of 20 mg/m2 intravenously over 4 h for five consecutive days (Day -15 to -11) followed by cytarabine of 10 mg/m2 q12 h for 7 days (Day -15 to -9), aclarubicin of 10 mg/day for 4 days (Day -12 to -9), and G-CSF 5µg/kg per day for priming until white blood count was >20 x109/L and immediately followed by myeloablative conditioning regimen (MAC) consisted with thymoglobulin (2.5mg/kg/day) which was administered for 3 days （Day -8 to -6), iv Bu (4 mg/kg in divided doses daily for 4 days) on days -5, -4, -3, and -2, iv Flu (30 mg/m2 once daily for 4 days, total dose 120 mg/m2) on days -5, -4, -3, and -2 and iv Melphlan (70 mg/m2 once daily for 3 days, total dose210 mg/m2) was performed on days -4 and -2.

Official Title
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Modified Post-Transplant Cyclophosphamide Combined With DCAG as a Bridge Followed by Busulfan, Fludarabine and Melphalan Based Conditioning Regimen for Children With Juvenile Myelomonocytic Leukemia

Conditions
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Hematopoietic System--Cancer

Intervention / Treatment
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* Drug: Decitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: JMML patients diagnosed in our center and with the indications of transplant without the suitable donor. Exclusion Criteria: JMML patients do not need to transplant.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Decitabine|Decitabine for injection|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease statue | Disease status can be measured by test the of (minimal residual disease) MRD, MRD<0,01% as negative. The quantitative of gene mutation is 0 as negative. | one months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSCT, PT/Cy, Decitabine, JMML