Allogeneic hematopoietic cell transplantation: from experimental biology to clinical care

Abstract

Purpose: For more than half a century, researchers have explored myeloablative, high-dose chemo/radiotherapy followed by allogeneic hematopoietic stem cell transplantation (HCT) for therapy of malignant and nonmalignant hematological diseases. Continuous advances in the field have changed this approach from one that was initially thought to be fraught by insurmountable complications to one that is now considered standard therapy for many diseases.

Methods: In order to extend allogeneic HCT to include elderly patients, who represent the main population affected by hematological malignancies, and to those who are medically unfit to undergo conventional HCT, novel non-myeloablative approaches have been developed. These approaches rely on graft-vs-tumor effects for tumor eradication rather than high-dose chemoradiotherapy, and, accordingly, have lower toxicities than conventional regimens.

Results: Results with non-myeloablative regimens have been gratifying, and this may change the future of allogeneic HCT. Advances could not have been possible without basic research and studies in pre-clinical animal models.

Conclusion: Further work is focused on improving graft-vs-tumor effects while achieving better control of graft-vs-host disease.

Fig. 1

Survival and disease-free survival of patients with chronic myelogenous leukemia (CML; a) and acute myelogenous leukemia (AML; b) receiving conditioning with either Bu or TBI combined with Cy (Socié et al. 2001) (Copyright American Society of Hematology, used with permission)

Fig. 2

Disease-free survivals of patients with hematological malignancies after HLA-matched related HCT, comparing patients with and without acute and chronic GVHD (Weiden et al. 1981) (Copyright 1981 Massachusetts Medical Society. All rights reserved)

Fig. 3

Nonmyeloablative regimens for HCT from HLA-matched related and unrelated donors (Baron et al. 2003) (Reprinted with permission from IMSS)

Fig. 4

Neutrophil and platelet changes in 212 patients with malignancies given HLA-matched related HCT after nonmyeloablative conditioning (Storb 2002) (Reprinted with permission from the American Society of Clinical Oncology)

Fig. 5

Comparisons of cumulative incidences of severe day-100 non-hematologic toxicities among HCT recipients given nonmyeloablative vs myeloablative conditioning. Shown are CTC grades 3–5 toxicities in the following organ systems: (a) gastrointestinal; (b) hepatic; (c) infection; (d) metabolic; (e) pulmonary; and (f) renal. Percentages of patients having organ-specific comorbidities before HCT are represented as open bars (□) for nonmyeloablative and as solid bars (■) for myeloablative recipients (Diaconescu et al. 2004) (Copyright American Society of Hematology, used with permission)