Non-myeloablative stem cell transplantation – pro
While the intensity of the regimens used for conditioning in conventional HDC varies, collectively they have been termed “myeloablative.” Several less intense conditioning regimens have been developed recently and rely more on immunosuppression than cytotoxic effects to permit engraftment of donor cells. These regimens, collectively termed “non-myeloablative”, also vary in intensity with substantial overlap between the ranges for “myeloablative” and “non-myeloablative” regimens. Studies have shown that donor allogeneic stem cells can engraft in recipients using less-intensive conditioning regimens that are sufficiently immunosuppressive to permit graft-host tolerance. This manifests as a stable mixed donor-host hematopoietic chimerism. Once chimerism has developed, a further infusion of donor leukocytes may be given to eradicate malignant cells by inducing a graft vs. tumor effect. Non-myeloablative allogeneic transplants, also referred to as “mini-transplant” or “transplant lite”, are thought to be potentially as effective as conventional HDC followed by an allogeneic stem cell transplantation (AlloBMT), but with decreased morbidity and mortality related to the less intense non-myeloablative chemotherapy conditioning regimen. Consequently, for patients with malignancies who are eligible for conventional HDC/AlloBMT, conditioning with milder, non-myeloablative regimens (NM-AlloBMT) represents a technical modification of an established procedure.
In terms of confitioning regimens, very few studies have compared different conditioning regimens. Insisting on a “proven” regimen would result in a situation in which approved transplants cannot be delivered because no specific used regimen is “proven”. As such, all but most novel conditioning regimens should be considered within standard of care.
Currently the situation is that guidelines support stem cell transplantation but do not indicate specific regimens for conditioning. Many different regimens are being used based on phase II study evidence and very few phase III trials have been performed. Excluding conditioning regimens on the basis that only phase II evidence si available would results in a paradoxical situation in which a guidelines recommended and admittedly medically necessary procedure cannot ever be performed because its basic constituent, conditioning, is denied as experimental. For this reason, I consider well supported regimens with good phase II data to be appropriate as a part of standard stem cell transplants.
Corradini P, Tarella C, Olivieri A, et al. Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies. Blood. 2002; 99(1):75-82.
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Punit D. Wadhwa et al, High-dose carmustine, etoposide, and cisplatin for autologous stem cell transplantation with or without involved-field radiation for relapsed/refractory lymphoma: An effective regimen with low morbidity and mortality Biology of Blood and Marrow Transplantation Volume 11, Issue 1 , Pages 13-22, January 2005
H F Fernandez et al, Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road? Bone Marrow Transplantation (2007) 40, 505–513
NCCN.ORG, Non-Hodgkin Lymphoma, http://nccn.org/professionals/physician_gls/PDF/nhl.pdf