Second allogeneic stem cell transplantation using nonmyeloablative conditioning for patients who relapsed or developed secondary malignancies following autologous transplantation.
OBJECTIVE
Second allogeneic stem cell transplants for hematological malignancies are associated with a high incidence of transplant-related mortality due to the cumulative incidence of toxicity of the high-dose chemoradiotherapy traditionally used as an essential component of the conditioning. We have demonstrated previously that nonmyeloablative conditioning for primary allogeneic transplants from both sibling and unrelated donors results in minimal transplant-related toxicity and excellent stem cell engraftment. This study explores the possibility of using nonmyeloablative conditioning to minimize transplant-related toxicity in patients who have undergone second allogeneic transplants.


METHODS
Twelve high-risk, heavily treated patients-five with acute myelogenous leukemia (AML); five with non-Hodgkin's lymphoma (NHL); one with Burkitt's lymphoma, and one with acute lymphoblastic leukemia (ALL)-underwent second allogeneic nonmyeloablative stem cell transplantation (NST) from human leukocyte antigen (HLA)-matched donors, 29 (median) (range 3-57) months following their first transplantation procedure. The conditioning consisted of fludarabine 30 mg/m(2) daily for 6 days, busulfan 4 mg/kg daily for 2 days, and anti-T-lymphocyte globulin 10 mg/kg daily for 4 days. Anti-graft-vs-host disease (anti-GVHD) prophylaxis consisted of cyclosporine A alone, 3 mg/kg.


RESULTS
Engraftment was observed in all recipients, with complete and stable chimerism. None of the patients developed veno-occlusive disease of the liver or multi-organ failure. Five very high-risk patients with NHL (n = 3), Burkitt's lymphoma (n = 1), and AML (n = 1) relapsed 2 to 6 months post-transplant, and four of them died. Six patients appear to be disease-free after median follow-up of 23 months. One additional patient died from grade IV hemorrhagic cystitis. Actuarial survival and disease-free survival at 34 months are 56% and 50% respectively, with 95% confidence interval (25-78%).


CONCLUSIONS
These results suggest that nonmyeloablative conditioning significantly reduces transplant-related toxicity, thus making a second transplant feasible.
Nagler
A
A
The Department of Bone Marrow Transplantation & The Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel. Nagler@hadassah.org.il
Or
R
R
Naparstek
E
E
Varadi
G
G
Slavin
S
S
D000206:Actuarial Analysis; D000293:Adolescent; D000328:Adult; D000818:Animals; D002423:Cause of Death; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000473:pathology; D020350:Graft vs Tumor Effect; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000150:complications / Q000628:therapy*; D012008:Recurrence; D015996:Survival Rate; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous / Q000009:adverse effects; D014184:Transplantation, Homologous; D016896:Treatment Outcome