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Allografting on outpatient basis can decrease GVHD prevalence, severity
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Allogeneic hematopoietic stem cell transplantation is an effective and potentially curative treatment for a variety of hematological diseases.
Reduced-intensity conditioning (RIC) has been developed to decrease regimen-related toxicity of allogeneic hematopoietic stem cell transplantation (allo-SCT) and to induce host-versus-graft transplantation tolerance with rapid engraftment of donor stem cells, subsequently diminishing graft-versus-host disease (GVHD).
Guillermo J. Ruiz-Argüelles
David Gómez-Almaguer
RIC is appropriate for the elderly and other high-risk patients who are otherwise ineligible to receive conventional allografts.
GVHD is still a major cause of morbidity and mortality after allo-SCT. The disease is a complication that may considerably limit the benefit of transplantation, and it develops in 30% to 70% of allo-SCT recipients who survive beyond 100 days. GVHD appears to be associated with the stem cell source and the conditioning regimen, among other variables.
Allogeneic peripheral blood stem cells represent an alternative source of hematoprogenitors, and they are associated with faster platelet and neutrophil recovery compared with bone marrow. Several reports have shown a higher incidence of chronic GVHD in transplants using peripheral blood stem cells, especially when large numbers of CD34+ cells are infused, making GVHD the leading cause of late nonrelapse mortality after transplantation.
A new approach
In developing countries, conventional transplantation using a special inpatient transplantation unit and standard myeloablative conditioning regimens is unaffordable for most patients. To overcome this problem, we have implemented changes in the therapeutic approach that have resulted in the simplification of performing allografts.
The use of RIC regimens for allografting by our group and others has resulted in a substantial reduction in cost, and because the cost of grafting peripheral blood stem cells is lower than the cost of allografting using bone marrow-derived stem cells, we elected to use peripheral blood stem cells and implement it as an outpatient procedure.
A number of studies — both randomized and nonrandomized — have reported a higher incidence of chronic GVHD among recipients of allogeneic peripheral blood stem cells from HLA-identical sibling donors. Other studies have suggested that the advent of RIC regimens has diminished the transplant-related mortality and lengthened the period during which acute GVHD can develop. In other reports, the use of RIC has diminished the overall incidence of acute GVHD without necessarily translating into a reduction in the incidence of chronic GVHD.
Data comparisons
In a recent publication, we reported about a group of 301 Mexican patients allografted using RIC and peripheral blood stem cells. The incidence of GVHD was lower than that reported using conventional myeloablative preparative regimens. Even more importantly, the severity of GVHD was lower and did not significantly affect the long-term survival of those patients who developed the disease. In addition — and as expected — we found a positive effect on the survival of patients with malignant disease, most likely as a result of the graft-versus-malignancy effect.
In our study, although many patients developed GVHD, 18% had grade-3/grade-4 acute GVHD and 19% had extensive chronic GVHD. These results are in contrast with those reported by other researchers using peripheral blood stem cells and conventional myeloablative conditioning regimens.
Some data suggest that the use of an outpatient procedure has a role in the incidence of acute GVHD. In Sweden, Svahn and colleagues studied the long-term follow-up of patients treated at home during the pancytopenic phase after myeloablative allogeneic stem cell transplantation and pointed out several advantages, including a reduced risk for acute GVHD. Seventeen percent of patients in the outpatient transplant group developed grade-2 to grade-4 acute GVD vs. 44% in the inpatient transplant group, and 52% of patients in the outpatient transplant group developed chronic GVHD vs. 57% in the inpatient transplant group.
In another study in Sweden, Petersen and colleagues studied 27 patients transplanted in an ambulatory setting using nonmyeloablative conditioning. Of them, 57% developed grade-2 to grade-4 acute GVHD, and 80% developed extensive chronic GVHD.
In Mexico, we found — as Svahn did — a low incidence of acute GVHD; however, the incidence of chronic GVHD in our publication was lower than they reported. Some possible explanations were postulated by Svahn and colleagues regarding the advantages of the outpatient procedure:
- There are fewer bacteria than in the in-hospital setting.
- Hospitalized patients are under stress, which may cause the release of cytokines triggering acute GVHD.
- At home, patients get more physical activity and move around the house more than they would an isolation room.
Interestingly, patients in our study had more physical activity because they were instructed to come to the hospital or medical office on a daily basis and were allowed to have a clean but “free” diet.
Conclusion
The higher incidence of GVHD reported in other studies after peripheral blood stem cell transplant seems to decrease if nonmyeloablative conditioning regimens are used.
We can speculate that the GVHD-promoting effect of the use of peripheral blood stem cells instead of bone marrow-derived stem cells is counteracted by the GVHD-sparing effect of both RIC and the outpatient conduction of the allograft, which in turn favor the low incidence and severity of GVHD.
Environmental factors seem to be critical in the development of GVHD and probably should receive more attention.
References:
- Cantu-Rodriguez OG. Eur J Haematol. 2011;87-521-530.
- Petersen SL. Br J Haematol. 2004;125:225-231.
- Svahn BM. Bone Marrow Transplant. 2005;36:511-516.
For more information:
- Guillermo J. Ruiz-Argüelles, MD, FACP, FRCP (Glasg), is director general of the Centro de Hematologia y Medicina Interna in the Clinica Ruiz in Puebla, Mexico, and clinical professor of hematology at Universidad Popular Autónoma del Estado de Puebla and Universidad de las Américas Puebla. He also is a member of the HemOnc Today Editorial Board. David Gómez-Almaguer, MD, is chief of the department of hematology of the Hospital Universitario de Nuevo León and clinical professor of hematology at Universidad Autónoma de Nuevo León. Disclosure: Drs. Ruiz-Argüelles and Gómez-Almaguer report no relevant financial disclosures.