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Investigators have reported favorable results of allogeneic hematopoietic stem cell transplant (HSCT) in a small study of patients with juvenile myelomonocytic leukemia (JMML).
The team said the positive outcomes may be a result of conditioning with busulfan and melphalan (BuMel) or the conventional-dose chemotherapy some patients received before HSCT.
Regardless, all 7 patients studied are in remission at more than 1 year of follow-up.
“The lack of transplant-related mortality in the group of children we studied . . . suggests that BuMel may represent a successful HSCT high-dose chemotherapy regimen,” said study author Hisham Abdel-Azim, MD, of Children’s Hospital Los Angeles in California.
“It is also possible that administering conventional-dose chemotherapy before HSCT to patients with more progressive disease may have contributed to the improved outcomes.”
Dr Abdel-Azim and his colleagues described this research in a letter to Blood.
Conventional chemo and transplant
The investigators retrospectively analyzed 7 JMML patients with a median age of 2.6 years at HSCT.
Five patients received conventional-dose chemotherapy before transplant. All of these patients received mercaptopurine. One received hydroxyurea as well, and another patient received fludarabine, cytarabine, and cis-retinoic acid.
As for transplant, 2 patients received a 10/10 HLA-matched related bone marrow graft, 1 received a 9/10 HLA-matched related bone marrow graft, 1 received a 9/10 HLA-matched unrelated bone marrow graft, and 3 patients received cord blood grafts.
The median total nucleated cell count was 4.2 × 108 cells/kg, and the median CD34 cell dose was 3.3 × 106 cells/kg.
Conditioning and GVHD prophylaxis
All 7 patients received backbone conditioning with BuMel: Bu at 1 mg/kg dose every 6 hours intravenously on days −8 to −5 (with therapeutic drug monitoring to achieve overall concentration steady state [CSS] of 800-1000 ng/mL) and Mel at 45 mg/m2 per day intravenously on days −4 to −2.
The median Bu CSS and area under the curve were 884 µg/L (range, 560-1096) and 1293 µmol/L-minute (range, 819-1601), respectively.
The patient with a 9/10 HLA-matched related graft received BuMel and fludarabine at 35 mg/m2 per day intravenously on days −7 to −4.
The patient with the 9/10 HLA-matched unrelated graft received BuMel and alemtuzumab at 12 mg/m2 intravenously on day −10 and 20 mg/m2 on day −9, with methylprednisolone at 2 mg/kg per day in divided doses during the alemtuzumab infusion.
The patients who received cord blood grafts received BuMel and rabbit antithymocyte globulin at 2.5 mg/kg per day intravenously on days −4 to −1. They also received methylprednisolone at 2 mg/kg per day in divided doses during antithymocyte globulin infusion, then tapered over 6 weeks.
All patients received tacrolimus as graft-vs-host disease (GVHD) prophylaxis. Patients who received bone marrow grafts also received methotrexate at 5 mg/m2 on days 3, 6, and 11.
Outcomes
The median time to neutrophil engraftment (≥500/mm3) was 20 days, and the median time to platelet engraftment (≥20 000/mm3) was 36 days.
Six patients (85.7%) achieved predominant (>95%) donor hematopoietic stem cell engraftment.
One patient who received a cord blood graft had autologous recovery at day 54. She went on to receive a related haploidentical HSCT on day 105. One hundred days later, she is in remission, with predominant donor chimerism.
The patient who received the 9/10 HLA-matched related graft developed grade 4 acute GVHD, followed by severe chronic GVHD that required bowel resection.
This patient and one of the patients who received a 10/10 HLA-matched related graft developed severe sinusoidal obstructive syndrome, which resolved with supportive care.
At a median follow-up of 25.3 months (range, 6-99.3), all 7 patients are in remission.
The investigators said their target Bu CSS may have contributed to the improved outcomes they observed, or pre-HSCT chemotherapy may have been a contributing factor. A prospective clinical trial could provide answers.
