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Outcomes of haploidentical bone marrow transplantation in infant acute leukemia: a single center experience

Bone Marrow Transplantation (2024)Cite this article

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Infant leukemia typically refers to the diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) in a child under 1 year of age. Interestingly, the occurrence of AML in infants is nearly equivalent to that of ALL, a contrast from the pattern seen in children older than 1 year in which ALL is five-fold more prevalent. Alterations in the lysine methyltransferase 2A gene (KMT2A) occur more commonly in infant leukemia than leukemia in older children. In fact, KMT2A rearrangements are found in 70–80% of ALL cases in infants compared to only 5–6% in older patients. While the AML survival rates in infants are similar to those of older children, the survival rates for infant ALL are significantly lower [1]. Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative for infant leukemia. Although there are several studies examining the use of haploidentical bone marrow transplantation (haplo-BMT) in children, there is a notable absence of reports focusing on its role specifically in infant leukemia. Total Body Irradiation (TBI) is considered a crucial component of the preparatory regimen for patients with ALL undergoing allo-HCT as it has shown to be superior to chemotherapy only regimens. However, the use of TBI in patients under 3 years of age is associated with a heightened risk of multi-organ dysfunction, including endocrine, metabolic, renal, ocular, central nervous system toxicity with neurocognitive defects, growth impairment and secondary malignancies. Therefore, TBI should be avoided in these young patients as its toxicity outweighs its therapeutic benefits. Hence, we have employed a busulfan, fludarabine, melphalan (BU-FLU-MEL) conditioning regimen for our younger ALL patients.

Between November 2019 and November 2023, a total of six patients underwent myeloablative T-cell replete haplo-BMT at our center (Table 1). Their median ages at diagnosis and at BMT were 3 and 12 months respectively. All patients received the same conditioning comprised of busulfan (BU) at 1–1.1 mg/kg q6h for a total of 12 doses (days −8 to −6) [2]. BU pharmacokinetics of the first dose were performed with the seventh and remaining doses modified resulting in cumulative exposures between 40 and 54 mg × h/l (Table 1). BU was followed by fludarabine (FLU) 30 mg/m2 for our first two transplants and FLU 40 mg/m2, for the later five, given on days −5 to −2 and a single dose of melphalan (MEL) 100 mg/m2 on day −2. GvHD prophylaxis consisted of post-transplant cyclophosphamide (PT-CY) 50 mg/kg on days +3 and +4, with IV tacrolimus and mycophenolate mofetil (MMF) starting on day +5. MMF was administered at a dose of 15 mg/kg q 8 h IV and in the absence of GvHD was discontinued on day +28. Due to difficulty in obtaining a liquid suspension of tacrolimus without the use of a compounding pharmacy, all patients were switched to oral cyclosporine A (CSA) just prior to hospital discharge. Tacrolimus was dose adjusted to maintain levels of 7–10 ng/ml and PO CSA targeted levels of 120–160 ng/ml. In the absence of GvHD, CSA was weaned starting from day +70 to +90 and discontinued by day +120. Grading of acute and chronic GvHD was performed based on the modified Glucksberg grading system.

Table 1 Patient, disease, transplant characteristics, outcomes, and complications.
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Acknowledgements

The authors wish to thank the inpatient and outpatient APPs, nursing and other staff on the pediatric HCTT unit at Diamond Children’s/Banner University Medical Center in Tucson for their outstanding care of our patients.

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Authors and Affiliations

  1. Department of Pediatrics, University of Arizona, Tucson, AZ, USA

    Dimitrios Filioglou, Laurel Truscott, Naresh Reddivalla & Emmanuel Katsanis

  2. The University of Arizona Cancer Center, Tucson, AZ, USA

    Laurel Truscott & Emmanuel Katsanis

  3. Department of Medicine, University of Arizona, Tucson, AZ, USA

    Emmanuel Katsanis

  4. Department of Immunobiology, University of Arizona, Tucson, AZ, USA

    Emmanuel Katsanis

  5. Department of Pathology, University of Arizona, Tucson, AZ, USA

    Emmanuel Katsanis

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  1. Dimitrios Filioglou
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  4. Emmanuel Katsanis
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Contributions

DF wrote the manuscript. LT and NR treated the patients prior to HCT and referred them for HCT and edited the manuscript. EK managed the patients throughout their HCT course, collected and analyzed the data and co-wrote the manuscript.

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Correspondence to Emmanuel Katsanis.

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Filioglou, D., Truscott, L., Reddivalla, N. et al. Outcomes of haploidentical bone marrow transplantation in infant acute leukemia: a single center experience. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02281-8

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