Hematopoietic stem cell transplantation for childhood myeloid malignancies after high-dose thiotepa, busulfan and cyclophosphamide

We evaluated the efficacy and safety of the conditioning regimen that consisted of TBI and melphalan (L-PAM), followed by hematopoietic SCT (HSCT) in 23 children with advanced hematological malignancies. The median age at HSCT was 9 (range, 2-15) years. The underlying diseases were ALL in 16 patients (5 in CR2, 3 in CR3, 6 in relapse (RP) and 2 in induction failure (IF)), AML in 4 patients (3 in RP and 1 in IF) and non-Hodgkin's lymphoma in 3 patients (1 in CR3, 1 in CR4 and 1 in RP). The stem cell sources were BM for 19 patients and cord blood for 4 patients. All patients received the conditioning regimen that consisted of TBI 12 or 13.2 Gy and L-PAM 210 mg/m 2 . In all, 22 patients engrafted on the median of day 16 (range, 10-23). The regimen was well tolerated and common regimen-related toxicities (RRTs) included grade II stomatitis and grade I hepatic toxicity. The cumulative incidences of RP and TRM were 47.6 and 21.5%, respectively. At a median follow-up of 24.4 months, the probability of disease-free survival was 41.0%. The regimen may provide sufficient anti-leukemic effect without increased RRT for advanced pediatric hematological malignancies.

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

TBI and melphalan followed by allogeneic hematopoietic SCT in children with advanced hematological malignancies

Inagaki

Nagatoshi

Sakiyama

et al. 2010

“…26,28,34 Some alternative regimens have been used and reported but failed to strongly demonstrate advantage because of a too small cohort or a higher number of early relapse and regimen-related deaths. 29,32,[35][36][37] Much progress was done in the HSCT field from 1990s: improvement in HLA typing, improvement of supportive care, more available immunosuppressive drugs, improvement in laboratory cellular therapy settings, better understanding and monitoring of minimal residual disease. However, we have to continue our efforts and research in order to improve global results, that is, disease control and both acute and late side effect.…”

Section: Discussionmentioning

confidence: 99%

Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Berranger

Cousien

Petit

et al. 2013

Allogeneic hematopoietic SCT (HSCT) appears to be an efficient tool to cure high-risk AML in first CR but the choice between BUbased or TBI-based conditioning regimens still remains controversial. In order to analyze the impact of conditioning regimen on long-term survival, we conducted a retrospective analysis from French registry data including all consecutive patients under 18 years old (n ¼ 226) from 1980 to 2004 transplanted for AML in CR1 from sibling (n ¼ 142) or matched unrelated donors and given either TBI-1200 cGy and CY 120 mg/kg (TBI-Cy, n ¼ 84) or BU 16 mg/kg and CY 200 mg/kg (BuCy200, n ¼ 142). Patient subgroups were comparable for all criteria except for median age at diagnosis and HSCT and for donor type. Both 5-year OS and disease-free survival (DFS) were significantly better in BuCy200 group (P ¼ 0.02 and 0.005, respectively). In multivariate analysis, both HLA matching and BuCy200 appeared as good prognostic factors for treatment-related mortality and DFS. Grade 2-4 acute GvHD and chronic GvHD rates were statistically higher in TBI-Cy group than in Bu-Cy200 one with a RR at 2 (P ¼ 0.002). In total, Bu-Cy200 conditioning regimen gives better outcome compared with TBI-Cy irrespective of the stem cell source and the donor type.

“…But pediatric conditioning regimens containing thiotepa were not reported to have an exceedingly high incidence of VOD. [30][31][32][33] Most recently a treatment regimen consisting of cyclophosphamide, thiotepa and carboplatin was assessed for the occurrence of VOD in adults. The calculated plasma concentration-time curves (AUCs) for cyclophosphamide and its activated metabolites showed that the incidence of VOD was rather linked to bioactivated cyclophosphamide than to the administration of thiotepa.…”

Section: Discussionmentioning

confidence: 99%

Stem cell transplantation in children with infantile osteopetrosis is associated with a high incidence of VOD, which could be prevented with defibrotide

Corbacioglu

Hönig

Lahr

et al. 2006

Malignant infantile osteopetrosis (MIOP) is a rare hereditary disorder of osteoclast function, which can be reversed by hematopoietic stem cell transplantation (SCT). We observed a high incidence of hepatic veno-occlusive disease (VOD) in transplanted patients and explored the prevention of this complication by using defibrotide (DF) as a prophylaxis. Twenty children with MIOP were consecutively transplanted in our center between 1996 and 2005. Eleven of these patients were transplanted between 1996 and 2001 and experienced an overall incidence of VOD of 63.6% (7/11). VOD was severe in three patients and one patient succumbed to VOD-related multi-organ failure. Owing to this very high incidence of VOD, DF prophylaxis was initiated in nine patients consecutively transplanted between 2001 and 2005. In this group, only one patient (11.1%) was diagnosed with moderate VOD. We report here a very high risk in patients with MIOP to develop VOD after transplantation. Prophylactic DF was implemented in our current transplant protocol and reduced the VOD rate significantly in this high-risk population.