Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation

Abstract

It is unknown whether the severity, timing, and quality of graft-versus-host disease (GVHD) may be different after nonmyeloablative as compared with myeloablative hematopoietic stem cell transplantation (HSCT). Therefore, GVHD incidence, morbidity of skin, liver, and gut, requirements for immunosuppressive therapy, and survival were retrospectively analyzed in 44 patients who underwent nonablative HSCT and 52 who underwent ablative HSCT (median ages, 56 and 54 years, respectively). The nonablative transplantation regimen consisted of low-dose total body irradiation (TBI), preceded in some patients by fludarabine administration and followed in all patients by immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Those who underwent myeloablative HSCT were prepared with different TBI-and non-TBIcontaining regimens and received CSP plus methotrexate or MMF for GVHD prophylaxis. The cumulative incidence of grades II-IV acute GVHD was lower after nonablative transplantation (64% vs 85%; P ‫؍‬ .001), but there were no differences in the cumulative incidence of chronic GVHD requiring treatment (73% vs 71%; P ‫؍‬ .96). Nonablative transplantation was associated with the delayed initiation of steroid treatment for GVHD (0.95 months vs 3.0 months; P < .001) and with the use of fewer systemic immunosuppressants in the first 3 months after transplantation (P < .04). This corresponded to more prevalent skin and more severe gut morbidity 6 to 12 months after nonablative transplantation. Our results show that nonablative HSCT is associated with a syndrome of acute GVHD occurring after day 100 in many patients. This "late-onset acute GVHD" should be taken into consideration in the design of prospective studies comparing GVHD resulting from the two types of transplantation procedures.

Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan

“…However, Grade III-IV acute GvHD was infrequent and none died from acute GvHD. The incidence of chronic GvHD was higher than that in our previous experience (56%) [32] or in other reports [31,33] even after considering inevitable differences in the ethnicity, GvHD prophylaxis and matching practice of HLA, or disease risk. G-CSF mobilized peripheral blood stem cells may have been associated with an increased incidence of GvHD, particularly in its chronic form [34,35].…”

“…Most importantly, patients undergoing RIST are usually older than those undergoing CIST, which leads to a higher risk for GvHD [36,37]. Early CyA withdrawal regulation to get speedy achievement of complete donor chimerism after RIST in our protocol might have influenced the increased incidence of Grade II-IV acute GvHD, which might have affected the rate of chronic GvHD [33,35,38,39]. Although severe GvHD will be unavoidable for some patients including MDS with poor prognostic factors [40,41], the balance between GvHD and GvL is a significant concern in RIST and we should seriously evaluate the type and tapering speed of immunosuppressive agents after RIST.…”

“…Twenty patients had at least one episode of infectious complications within the first 100 days, with a total of 44 documented episodes (median, 2; range, 1-7 episodes) within the first 100 days after transplantation. These included proven bacterial infection (1 episode), suspected bacterial infection (1), suspected fungal infection (2), cytomegalovirus antigenemia (6), HSV infection (1), suspected viral infection (1), and uncertain causes (33). All infectious complications were recovered with or without appropriate antibiotic therapy.…”

Allogeneic hematopoietic stem cell transplantation (HSCT) after reduced intensity conditioning

“…Most have shown a lower incidence of acute GVHD (when acute GVHD was defined as GVHD occurring before day 100) but a similar incidence of chronic GVHD with RIC regimens [18]. The relatively reduced incidence and severity of acute GVHD after RIC transplantation can be explained by the combination of low-intensity pre-transplant conditioning and the initial mixed chimerism that may favor both host-versus-graft and graft-versus-host tolerance [17,18]. However, a number of patients given RIC conditioning experience late acute GVHD (i.e.…”

“…However, a number of patients given RIC conditioning experience late acute GVHD (i.e. acute GVHD occurring after day 100), often at the time of conversion from mixed to full donor Tcell chimerism [13,18].…”