Reduced-intensity conditioning hematopoietic stem cell transplantation: looking forward to an international consensus

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The treatment for hematological malignancies has excelled over the past decade. A vast number of hema-tological malignancies are now amenable to cure with hematopoietic stem cell transplants (HSCTs) [1]. Older patients with comorbidities are poor candidates for standard myeloablative conditioning (MAC). While myeloablative therapy remains the standard curative conditioning regimen in the treatment of malignant disorders such as acute myeloid leukemia, its use is limited to patients in the younger age group, and to those in good physical health. Therefore, the older population is generally unsuited to this form of treatment, even though most hematological malignancies are often diagnosed at the age of 70–80 years. The advent of reduced-intensity conditioning (RIC) has provided these patients with a viable treatment option. Prior to undergoing HSCT, patients are treated with a conditioning regimen. This not only decreases the tumor burden, but also maximizes the capability of the donor cells to engraft successfully by suppressing the patient's immune system. Conditioning regimens vary in the amount of agent used. These compounds are often used at highly toxic dosage levels that are required to induce an immunocompromised state through a cytoreductive effect [2]. Over the past decade, conditioning regimens have considerably evolved with the development of RIC. These regimens are composed of reduced doses of cytotoxic agents in addition to a T-cell depleting agent [3]. The most commonly used regimens include fludarabine in combination with low-dose total body irradiation, or an alkylating agent such as busulfan, cyclo-phosphamide, or melphalan [3]. This treatment modality relies on a graft-versus-leukemia effect and has minimal associated toxicity. It is difficult to define RIC as it falls into an intermediate category between the MAC and the non-myeloablative regimens, since it does result in prolonged pancytopenia. Sources of donor cells include peripheral blood stem cells, bone marrow, and umbilical cord blood. Peripheral blood stem cells are more commonly used owing to the decreased engraftment time associated with their use [4]. Umbilical cord blood stem cells are a promising alternative source of stem cells with an associated 1-year survival rate of up to 40%, and a 9% incidence of grade III-IV acute graft-versus-host disease (GVHD). However, studies have also reported a transplant-related mortality (TRM) rate of 39– 48% associated with use of umbilical cord blood stem cells [5, 6]. Studies assessing the influence of …