Christopher J Forlenza, MD
,
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY
Rachel Kobos, MD
,
Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY
Nancy A Kernan, MD
,
Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY
Andromachi Scaradavou, MD
,
New York Blood Center, New York, NY
Susan E. Prockop, MD
,
Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY
Kevin Curran, MD
,
Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY
Neerav Shukla, MD
,
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY
Peter G Steinherz, MD
,
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY
Richard O'Reilly, MD
,
Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY
Farid Boulad, MD
,
Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan-Kettering Cancer Center, New York, NY
The standard of care for the transplantation of pediatric patients with acute leukemia and prior CNS disease is the use of total body irradiation (TBI), plus a CNS radiation therapy (RT) boost. However, the late effects of radiation can be prohibitive, especially in younger children or those who have previously received radiation therapy. We developed a chemotherapy-only cytoreductive regimen with the intent of targeting the CNS with agents that can readily cross the blood brain barrier and achieve high concentrations. We used the combination of Busulfan (1mg/kg every 6 hours x 3 days), melphalan (50mg/m
2/day x 2 days), and thiotepa IV (8.3mg/kg/day or 250mg/m
2/day x 2 days).
We treated six patients with acute myelogenous leukemia (AML (N=5) or acute lymphoblastic leukemia (ALL) with this regimen from July 1999 and February 2013. The median age at the time of HSCT was 2.8 years (range 1.7 to 13.4 years). Patients were in complete CNS remission (CR) CR1 (N=1), CR2 (N=3), CR3 (N=1), and CR8 (N=1). All six patients were treated with multiple intrathecal chemotherapy agents prior to transplant. Four of six patients received cranio-spinal radiation therapy (RT) prior to HSCT; RT was required to achieve a CNS CR in 3 of 4 of these patients. One patient received CNS RT post HSCT, while one patient was completely spared CNS RT.
Donors and grafts included unrelated mismatched umbilical double cord transplants (N=4) and matched related T-cell depleted bone marrow transplants (N=2). All six patients engrafted. One patient succumbed to infectious complications nearly 2 months post HSCT. The five other patients are still alive without marrow or CNS relapse at a median follow-up of 19.4 months post HSCT (range: 11.1 to 149.5 months) .
While this represents a small patient series, this data provides evidence for a promising transplant chemotherapy-only regimen for the transplantation of pediatric patients with acute leukemia and CNS disease who are unable to receive TBI, and will be the focus of a larger prospective study.
