Nonmyeloablative Allogeneic Stem-Cell Transplantation for Hematologic Malignancies: A Systematic Review

Benjamin Djulbegovic, MD, PhD, Jerome Seidenfeld, PhD, Claudia Bonnell, BSN, MLS, Ambuj Kumar, MD, MPH

Cancer Control. 2003;10(1) 

In This Article

Objectives

Patient disease was categorized by AML, ALL, HD, NHL, CML, or MM ineligible for HDC/allo-SCT. This category included patients older than 55 years of age and those with concurrent diseases or conditions that increased the risk of treatment-related toxicity. Each hematologic malignancy was considered as a separate indication.

NM-allo-SCT entails administering reduced-intensity preparative regimens for allo-SCT that provide sufficient immunosuppression against host cells before transplants and against host and donor cells after transplants, with the net effect of establishing mutual graft-host tolerance to yield stable mixed donor-host hematopoietic chimerism. The goal of establishing chimerism is to allow the safe administration of donor-lymphocyte infusion to eradicate malignant cells. To date, NM-allo-SCT has been used predominantly in hematologic malignancies. Since so few studies reported using this technology in solid tumors, our systematic review focused on the safety and efficacy of NM-allo-SCT in hematologic malignancies.

Alternatives to NM-allo-SCT for patients with AML, ALL, HD, NHL, or MM ineligible for HDC/allo-SCT include HDC followed by autologous stem-cell transplantation (HDC/auto-SCT) and conventional-dose treatment. For patients with CML who are ineligible for HDC/allo-SCT, conventional-dose therapy (with imatinib mesylate [Gleevec]) is an alternative to NM-allo-SCT.

The goal of NM-allo-SCT is to improve the duration of survival either by directly altering the course of dis-ease or by increasing the time to relapse or progression and thus forestalling the natural progression. Intermediate outcomes related to the effects of treatment on disease -- complete remission, partial remission, and relapse rate -- were also considered. Since NM-allo-SCT attempts to induce tolerance between the recipient and donor, data on mixed chimerism are also of interest. Adverse health outcomes of NM-allo-SCT are treatment-related morbidity and mortality, including the incidence or prevalence of acute and chronic GVHD, veno-occlusive disease, and grade III/IV toxicity according to the National Cancer Institute toxicity criteria.

Does NM-allo-SCT improve the net health outcome of patients with AML, ALL, HD, NHL, CML, or MM who are ineligible for HDC/allo-SCT? Net health outcome includes an analysis of disease-free survival or overall survival balanced against treatment-associated toxicity, acute and chronic complications, and death. Results were compared with the natural history of each disease or the expected outcome of conventional treatment in patients with advanced hematologic malignancies.

Compared to treatment with the established alternatives, does NM-allo-SCT improve the net health out-come of patients with AML, ALL, HD, NHL, CML, or MM who otherwise are eligible for HDC/allo-SCT? Again, net health outcome includes an analysis of disease-free survival or overall survival balanced against treatmentrelated toxicity, complications, and death.

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