Use of a reduced-intensity conditioning regimen for allogeneic transplantation in patients with chronic myeloid leukemia

Summary:Reduced intensity preparative regimens are increasingly used for conditioning prior to allogeneic stem cell transplantation. As opposed to classical methods of pretransplant conditioning, patients receive predominantly immunosuppressive therapies that facilitate early engraftment, while cells within the graft itself promote continuation of the engraftment process. Despite early hopes that this form of transplant would be devoid of grade III and IV acute toxicities, there is a substantial amount of shortterm morbidity associated with the technique. Although long-term follow-up is not yet available, it is hoped that these regimens will spare young patients many of the late effects (cataracts, growth retardation, endocrine and reproductive problems) that are often associated with classical pre-transplant conditioning regimens. Reliable engraftment and leukemic control have been demonstrated in a large number of both adult and pediatric transplant recipients of these regimens, many of whom were deemed at high risk for standard conditioning because of serious co-morbidities, previous autologous transplantation or multiply relapsed disease. A brief review of the state of the art of this technology as it applies to pediatric transplantation is presented. Preliminary results of a survey of pediatric transplant centers indicate that a variety of protocols are used for a variety of indications. The use of standardized criteria for implementation of reduced intensity preparative regimens, the use of a limited number of regimens, and more extensive data collection will permit the elaboration of prospective comparative studies of this new and exciting modality. Bone Marrow Transplantation (2005) 35, S39-S43.

Section: How Does Donor Engraftment Occur Following Rit?mentioning

confidence: 99%

The hope and the reality of reduced intensity transplants in children with malignant diseases

Stein

Dini

Yaniv

2005

“…Our data and that from others indicate that RIST is effective for allografting individuals with CML; [6][7][20][21][22][23][24][25] despite the fact that most studies with reduced-intensity conditioning have a relatively short follow-up, there is information indicating that the procedure has a lower prevalence and severity of GVHD, 26 and similar efficacy to conventional allografting; the low prevalence of chronic GVHD in this study supports this observation, which may be related to the diminished organ damage induced by the conditioning schedule. Since this method is more feasible and affordable for patients and physicians in developing countries, the number of allografts in these places has increased substantially, as well as the publications related to bone marrow transplantation stemming from places where this therapeutic maneuver was considered as unaffordable previous to the development of this technology.…”

Section: Discussionmentioning

confidence: 88%

The early referral for reduced-intensity stem cell transplantation in patients with Ph1 (+) chronic myelogenous leukemia in chronic phase in the imatinib era: results of the Latin American Cooperative Oncohematology Group (LACOHG) prospective, multicenter study

Ruíz‐Argüelles

Gómez‐Almaguer

Morales-Toquero

et al. 2005

Summary:Using a reduced-intensity stem cell transplantation (RIST) schedule, 24 patients with Philadelphia (Ph1) ( þ ) chronic myelogenous leukemia (CML) in first chronic phase (CP) were prospectively allografted in four Latin American countries: Me´xico, Brazil, Colombia and Venezuela, using HLA-identical siblings as donors. The median age of the patients was 41 years (range 10-71 years); there were eight females. Patients received a median of 4.4 Â 10 6 /kg CD34 cells. The median time to achieve above 0.5 Â 10 9 /l granulocytes was 12 days, range 0-41 days, and the median time to achieve above 20 Â 10 9 /l platelets was also 12 days, range 0-45 days. In all, 22 patients are alive 81-830 (median 497) days after RIST. The 830-day probability of survival is 92%, and the median survival has not been reached, being beyond 830 days. A total of 11 patients (46%) developed acute graftversus-host disease (GVHD), and seven of 23 (30%) developed chronic GVHD. Two patients died 43 and 210 days after RIST, one as a result of sepsis and the other of chronic GVHD. The 100-day mortality was 4.4%, and transplant-related mortality was 8%. RIST for patients with CML in CP appears to be an adequate therapeutic option.

“…Incidence over 25% has been reported in many series, a number that needs to be understood in the context of the high-risk population that is usually selected for this type of procedure. Although patient costs of RIT are probably lower than those associated with myeloablative transplant, overall costs may be surprisingly high 6 due to delayed onset of severe infections including EBV reactivation. 7 As compared with standard conditioning, the incidence and severity of acute GvHD following RIT is lower in most published series; however, the incidence and severity of chronic GvHD was reported to be higher and tended to occur later.…”

Section: Resultsmentioning

confidence: 99%

Reduced-intensity conditioning in children: a reappraisal in 2008

Yaniv

Stein

2008

Transplant-related mortality and morbidity (both short and long term) have limited the effectiveness of SCT in children with both malignant and nonmalignant diseases. Reducedintensity preparative regimens permit engraftment of allogeneic cells without many of the toxicities associated with standard TBI-and non-TBI-based conditioning. We review the concepts that underlie reduced-intensity transplantation (RIT) and highlight the experience of the technique in children. Although acute organ damage may be reduced after these transplants, the overall incidence of severe infections and of GvHD may be similar to that seen after standard-intensity transplantation. The relatively small numbers of children who have received RIT and the newness of the technique preclude long-term follow-up with which to monitor the incidence of associated long-term side effects and disease-free survival. Future refinements in RIT and appropriate patient selection for these procedures will hopefully extend its utility in the future.