In recent years, umbilical cord blood (UCB) has widely been used as an alternative hematopoietic stem cell (HSC) source to treat various hematologic disorders in adults. UCB has several advantages over other HSC sources, including rapid availability, and lower or comparable incidence of severe acute graft-versus-host disease even with HLA-mismatched units. However, a high incidence of engraftment failure and early non-relapse mortality preclude UCB from use as a primary HSC source. A unique aspect of UCB transplantation (UCBT) is that Asian countries, particularly Japan, are leading the world in the number of UCBT procedures. This review is intended to give an update of UCBT outcomes in adults and problems to be solved, particularly focusing on engraftment failure.
The use of reduced-intensity conditioning has expanded the eligibility of hematopoietic cell transplantation (HCT) to older patients. In addition to reduced-intensity conditioning, increased availability of alternative donors including HLA mismatched unrelated donors have improved the safety as well as access of allogeneic HCT for a larger number of patients. However, acute graft versus host disease (GVHD) remains a lethal complication even in HLA - matched donor - recipient pairs and there is currently no standard treatment of patients with steroid refractory GVHD. The pathophysiology of GVHD fundamentally depends upon aspects of adaptive immunity and interactions between donor T cells and host dendritic cells. Recent work has revealed that the role of other immune cells or endothelial cells and components of the innate immune response are also important. Based on understanding of the pathophysiology of acute GVHD, multitarget therapy and cell therapy may open a new area for future therapeutic approaches.
Objective:The role of allogeneic hematopoietic stem cell transplantation (allo-SCT) for plasma cell myeloma (PCM) is still controversial. We investigated the effectiveness of reduced-intensity conditioning (RIC) allo-SCT in patients with PCM. Patients and Methods:We retrospectively studied a series of 10 PCM patients who underwent allo-SCT using reducedintensity conditioning (RIC) mainly consisting of fludarabine, busulfan, and low-dose total body irradiation from 2001 to 2006 in our single center. Of the 10 patients, 7 received allo-SCT from an HLA-matched related donor, 2 from an HLAmatched unrelated donor, and 1 from an HLA-2-mismatched unrelated donor. Results:All patients showed leukocyte and platelet engraftment. Seven patients developed grade II ― III acute graft-versushost disease (GVHD), and 4 developed extensive chronic GVHD. With a median follow-up of 90 months, the 5-year progression-free and overall survival rates were 34% and 69%, respectively. Six patients survived for more than 7 years after allo-SCT, and 3 of them are currently in continuous complete response (CR). Five of the 6 long-term survivors received allo-SCT from an HLA-matched related donor during the first remission within 10 months after the diagnosis.However, 4 patients who died of transplant-related toxicity or progressive disease received allo-SCT with relapsed disease more than 20 months after the diagnosis. Conclusion:These results suggested that RIC allo-SCT for PCM has the potential to result in a long-term CR if allo-SCT is performed during the remission of PCM in an early period after the diagnosis.
A 34-year-old woman with IgA-λ type multiple myeloma was treated with combination chemotherapy followed by highdose chemotherapy supported by autologous stem cell transplantation (SCT), and then underwent allogeneic SCT from an unrelated donor. Although she achieved a complete response, the disease relapsed 7 months after allogeneic SCT and lenalidomide was initiated. Nine days after starting lenalidomide, she complained of diarrhea and nausea. Colonoscopy showed edematous and erosive changes on colonic epithelium mucosa, and histological findings were consistent with graft-versus-hostdisease (GVHD). Lenalidomide was discontinued and glucocorticoid was initiated, resulting in a prompt resolution of the symptoms. Although sporadic cases of GVHD after initiating lenalidomide in allogeneic SCT recipients have been reported, such case has not been reported from Japanese population. Physicians should be aware of the possibility of developing GVHD by the administration of lenalidomide after allogeneic SCT.