Fludarabine allows dose reduction for total body irradiation in pediatric hematopoietic stem cell transplantation.
OBJECTIVE
To examine, in the setting of total body irradiation (TBI) for the preparation of pediatric hematopoietic stem cell transplantation (HSCT), whether TBI dose can be reduced without compromising the efficacy of a regimen consisting of fludarabine and radiotherapy; and whether there is any increased risk of pulmonary toxicity due to the radiosensitizing effect of fludarabine.


METHODS
A total of 52 pediatric patients with hematologic malignancies received TBI-based conditioning regimens in preparation for allogeneic HSCT. Twenty-three patients received 12 Gy in 4 daily fractions in combination with cyclophosphamide, either alone or with other chemotherapeutic and biologic agents. Twenty-nine patients received 9 Gy in 3 fractions in conjunction with fludarabine and melphalan. Clinical and radiation records were reviewed to determine engraftment, pulmonary toxicity (according to Radiation Therapy Oncology Group criteria), transplant-related mortality, recurrence of primary disease, and overall survival.


RESULTS
The two groups of patients had comparable pretransplant clinical characteristics. For the 12-Gy and 9-Gy regimens, the engraftment (89% and 93%; p = 0.82), freedom from life-threatening pulmonary events (65% and 79%; p = 0.33), freedom from relapse (60% and 73%; p = 0.24), and overall survival (26% and 47%; p = 0.09) were not statistically different.


CONCLUSIONS
The addition of fludarabine and melphalan seems to allow the dose of TBI to be lowered to 9 Gy without loss of engraftment or antitumor efficacy.
Kornguth
David G
DG
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1840 Old Spanish Trail, Houston, TX 77054, USA. dkorngut@mdanderson.org
Mahajan
Anita
A
Woo
Shiao
S
Chan
Ka Wah
KW
Antolak
John
J
Ha
Chul S
CS
D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D019337:Hematologic Neoplasms / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014916:Whole-Body Irradiation
D019653:Myeloablative Agonists; D011838:Radiation-Sensitizing Agents; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan