Forodesine treatment and post-transplant graft-versus-host disease in two patients with acute leukemia: facilitation of graft-versus-leukemia effect?
This article presents two case studies of patients diagnosed with T-cell acute lymphoblastic leukemia who relapsed following allogeneic hematopoietic stem cell transplantation and were subsequently enrolled in a clinical trial in which they received forodesine hydrochloride, a rationally designed, potent, transition-state inhibitor of purine nucleoside phosphorylase. Forodesine induced complete remission in both patients. Graft-versus-host disease developed subsequently but was treated successfully with conventional immunosuppressive therapy. Both patients remain in complete remission at the most recent follow-up. We hypothesize that forodesine contributed to a primary anti-leukemic cytotoxic effect as well as a secondary immunologic effect by allowing the development of an ongoing graft-versus-leukemia effect in these patients.
Gore
Lia
L
Section of Hematology/Oncology/BMT, Department of Pediatrics, University of Colorado School of Medicine and The Children's Hospital, Denver, CO, USA. Lia.Gore@UCHSC.edu
Stelljes
Matthias
M
Stelljes
Mattias
M
Quinones
Ralph
R
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D020544:Graft vs Leukemia Effect / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000628:therapy; D011684:Purine Nucleosides / Q000627:therapeutic use*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D011744:Pyrimidinones / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011684:Purine Nucleosides; D011744:Pyrimidinones; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase