Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin's disease.
Six patients with advanced Hodgkin's disease in which multiple conventional treatments (median prior chemotherapy regimens: seven), radiation therapy, and a prior autologous stem cell transplantation (SCT) had failed underwent allogeneic SCT following a fludarabine-based conditioning regimen. Median age was 29 years (22-30). Median time to progression after autologous SCT was 6 months (4-21). Disease status at transplant was refractory relapse (n = 3) and sensitive relapse (n = 3). Cell source was filgrastim-mobilized peripheral blood stem cells from an HLA-identical sibling (n = 4) or matched unrelated donor marrow (n = 2). Conditioning regimens were fludarabine-cyclophosphamide-antithymocyte globulin (n = 4), fludarabine-melphalan (n = 1) and fludarabine-cytarabine-idarubicin (n = 1). Myeloid recovery was prompt, with an absolute neutrophil count > or =500/microl on day 12 (11-15). Median platelet recovery to > or =20000/microl was on day 9 (0-60). Chimerism studies on day 30 indicated 100% donor-derived hematopoiesis in 4/5 evaluable patients (4/4 non-progressors). All responders (3/3) have ongoing 100% donor-derived chimerism. Acute graft-versus-host disease (GVHD) was diagnosed in 4/6 evaluable patients. Chronic GVHD was present in 2/4 evaluable patients. There were no regimen-related deaths. Overall day 100 transplant-related mortality was 2/6 (33%). Three patients have expired and three are alive and progression-free with a median follow-up of 9 months (6-26) post transplant. We conclude that allogeneic stem cell transplantation with fludarabine-based preparative regimens is feasible in these high-risk, heavily pretreated HD patients.
Anderlini
P
P
Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Giralt
S
S
Andersson
B
B
Ueno
N T
NT
Khouri
I
I
Acholonu
S
S
Cohen
A
A
Körbling
M J
MJ
Manning
J
J
Romaguera
J
J
Sarris
A
A
Rodriguez
Hagemeister
F
F
Mclaughlin
P
P
Cabanillas
F
F
Champlin
R E
RE
D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006689:Hodgkin Disease / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D003561:Cytarabine; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan; D015255:Idarubicin