Comparative outcome of hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia following cyclophosphamide and total body irradiation or VP16 and total body irradiation conditioning regimens

Abstract

To compare the outcome of hematopoietic stem cell transplantation (HSCT) in pediatric acute lymphoblastic leukemia (ALL) conditioned with two different regimens:(1) single dose of VP16 (60 mg/kg over 4 h) and total body irradiation (TBI; 1200 cGy, in six fractions) or (2) Cyclophosphamide 50 mg/kg over 1 h daily for 4 days followed by the same dose of TBI. One hundred and seven children with ALL received fully matched HSCT from 1990 to 2003 in the Hospital for Sick Children, Toronto. All received cyclosporin A and a short course of methotrexate for graft-versus-host disease (GVHD) prophylaxis. The VP16 group, there were 36 matched related donor transplants (MRD) and 26 matched unrelated donor transplants (MUD), and in the cyclophosphamide group there were 23 MRD and 22 MUD transplants. Neutrophil engraftment occurred at a median of 18 and 17 days for the VP16/TBI and the CY/TBI groups, respectively. The 3 year event-free survival and overall survival were 4777 and 5577% for those receiving VP16/TBI, and 5178 and 5378% for the CY/TBI group. There were no significant differences in the prevalence of acute or chronic GVHD and transplant-related mortality between the two groups. Both VP16/FTBI and CY/FTBI regimen are equally effective regimens.

Hematopoietic stem cell transplantation for pediatric autoimmune disease: where we stand and where we need to go

“…It is difficult to imagine putting a patient through an already risky procedure, which, if successful, carries with it a more than 50% chance of substituting one autoimmune disease for another. 69 …”

“…The specter of chronic GVHD after allogeneic transplantation is often interpreted as substituting one autoimmune disease with another. 69 There is an even less acceptable risk in patients who survive their immediate transplant but have relapse of their primary disease in the setting of full donor chimerism. 50 Finally, given the real risks of treatment-related morbidity and mortality associated with HSCT, the consideration of HSCT in patients with autoimmune disease is perpetually delayed as newer biologic agents such as TNF antagonists, costimulation blockers, cytokine inhibitors, and the like (reviewed in Moss and Isenberg 77 ) are introduced to the community on a regular basis.…”

“…73 Survivors, especially those requiring ongoing treatment, carry with them lifelong burdens from the diseases and their treatments. 3 Although the hematology/oncology community is willing to 'tolerate' a degree of accelerated TRM with transplantation in the setting of diseases that are ultimately lethal, 69,[74][75][76] the rheumatology community is generally dealing with diseases where the short-term risk of mortality is less than that of a 'standard' myeloablative transplant and where the long-term outcomes of conventionally treated patients may be quite variable. These concerns become even more heightened when allogeneic transplants are considered.…”

Conditioning regimens for acute lymphoblastic leukaemia allografts

“…In agreement with the CIBMTR results, in our study there was a trend towards more relapse for children conditioned with cyclophosphamide receiving matched sibling allografts compared to VP16 (65 vs 41%, P ¼ 0.2) with a comparable probability of acute and chronic graftversus-host disease (GVHD), Tables 2 and 3. 1 Nonetheless, for unrelated allografts recipients, the effect was the opposite with less relapse and more probability for acute and chronic GVHD in the cyclophosphamide group compared to the VP16 group resulting in better 3-year event-free survival for the cyclophosphamide group compared to the VP16 group (64 vs 49%), Tables 2 and 3. 1 It is difficult to extract conclusions from nonsignificant values.…”

“…It was interesting to read the recent paper by Gassas et al 1 comparing cyclophosphamide and VP16 containing conditioning regimens for children with acute lymphoblastic leukaemia (ALL). I was surprised that the authors did not cite the recent very large Centre for International Blood and Marrow Transplant Research (CIBMTR) study on precisely the same topic.…”