Mini-allografts' for haematological malignancies: an alternative to conventional myeloablative marrow transplantation.
BACKGROUND
Considerable morbidity and mortality are consequences of the myeloablative chemoradiotherapy utilised in conventional allogeneic marrow transplantation. This has generally restricted such potentially curative treatment to patients <50-55 years with normal organ function. Recent studies suggest that purine-analogue based non-myeloablative regimens are sufficiently immunosuppressive to facilitate allogeneic donor cell engraftment.


OBJECTIVE
To review the outcome of HLA-compatible sibling allogeneic peripheral blood progenitor cell (PBPC) transplants using fludarabine-based conditioning in patients ineligible for a conventional transplant, with emphasis on engraftment, graft vs host disease (GVHD) and graft vs tumour effects.


METHODS
Eleven patients (nine > or = 47 years age) with advanced haematological malignancies received one of three different fludarabine-based chemotherapy followed by infusion of granulocyte colony-stimulating factor mobilised PBPC. Cyclosporin-methotrexate was used as GVHD prophylaxis.


RESULTS
Two patients died early; minimal non-haematological toxicity apart from mucositis occurred in the other nine. Eight of the nine evaluable patients had evidence of durable donor cell engraftment in preference to recipient cells. Acute GVHD (> or = grade 2) occurred in seven of eight patients with donor engraftment who survived beyond two months. Four patients are alive in complete remission 8-28 months post-transplant; another is alive in probable remission at four months.


CONCLUSIONS
Fludarabine-based non myeloablative chemotherapy facilitates rapid engraftment of allogeneic donor cells, which produce powerful GVHD and graft vs tumour effects. This approach has the potential to extend the applicability of allogeneic stem cell transplants to patients traditionally regarded as too old or sick for conventional marrow transplants.
Grigg
A
A
Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Vic.
Seymour
J F
JF
Roberts
A
A
Szer
J
J
D000328:Adult; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D019337:Hematologic Neoplasms / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine