Objective: To investigate if low dose total body irradiation (TBI, 6.0-9.0 Gy) combined with intensified chemotherapy followed by autologous peripheral blood stem cell transplantation results in better survival in children with refractory leukemia or solid tumors.
Methods: Twenty-one children with malignant tumors were included in this study. There were 14 males and 7 females aged 3.5-12 years. Underlying disease included high-risk acute lymphoblastic leukemia (ALL, CR1 in 3 children and CR2 in 5 children), acute myeloblastic leukemia (AML, 9 children), non-Hodgkin's lymphoma stage IV (2 children), and neuroblastoma stage IV (2 children). The peripheral hematopoietic stem cells were collected six to eleven months after complete response, mobilized with high dose chemotherapy alone or combined with GM-CSF or G-CSF. The conditioning regimen consisted of chemotherapy with two to three combinations of the following drugs: cyclophosphamide, arabinosylcytosine, McNU, etopside, and ldarubicin on the basis of TBI (6.0-9.0 Gy). A mean of (1.8 +/- 0.5) x 10(8)/kg autologous mononuclear cells were transplanted. The patients were followed up after transplantation.
Results: Severe bone marrow suppression occurred in all patients around day +7. Peripheral white blood cell count decreased to 0 in all patients at day +4.8 +/- 2.9, and platelet count decreased to less than 20 x 10(9)/L at day +9.0 +/- 2.6. Successful engraftment was achieved in 21 patients, but four died of infection at day +17, +20, +31 and +67, respectively. Recovery of white blood cell (WBC) to 10 x 10(9)/L, absolute neutrophil count to 0.5 x 10(9)/L, platelet count to 20 x 10(9)/L occurred on 21 +/- 12, 26 +/- 13, and 27 +/- 10 days, respectively. During the follow up period, three patients relapsed at months, +1.5 years, and +2 years 10 months, respectively. One patient died of intracranial hemorrhage at +8 months. Thirteen patients had event-free survival for 2-12 years, with a mean of 6.7 +/- 3.4 years.
Conclusion: Our preliminary data suggest that myeloablative therapy with low dose TBI (6.0-9.0 Gy) combined with intensified chemotherapy followed by autologous peripheral blood stem cell transplantation might be associated with favorable results in children with refractory leukemia or solid tumors.