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Allogeneic Stem Cell Transplant with TBI/CY/Cytarabine Conditioning for Childhood Philadelphia-Positive ALL

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 22 de marzo del 2007

Presenter: Yoo, K.H.
Presenter's Affiliation: Samsung Medical Center, Korea
Type of Session: Scientific

Background

Allogeneic stem cell transplantation (ASCT) is generally felt to be the optimal curative treatment of Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL). The standard conditioning regimen to prepare these patients for transplant typically includes cyclophosphamide and total body irradiation. High-dose cytarabine (HDC) has been employed to treat patients with ALL who have relapsed or have been refractory to the standard induction chemotherapy. The authors proposed this study based on the hypothesis that adding HDC to the standard conditioning regimen may reduce the relapse rate by more thoroughly eradicating residual leukemia before transplant. This study describes the feasibility of a HDC-containing conditioning regimen for the treatment of children with Ph+ ALL.

Materials and Methods

• Prospective trial conducted at three cooperative institutions
• 13 consecutive patients with Ph+ ALL who received ASCT were enrolled
• Ages ranged from 3.5 - 15.8 years (median 12.2 years)
• Two patients (15.4%) were not in complete remission (CR) at time of transplant.
• The sources of stem cells were as follows:
  • unrelated BM (n=6)
  • unrelated cord blood (n=5)
  • matched sibling BM (n=2)
• The conditioning regimen included:
  • HDC (3 g/m2/dose every 12 h x 4 doses)
  • cyclophosphamide (60 mg/kg/d x 2 d)
  • total body irradiation (TBI)
• TBI was delivered in three different manners according to the each institutional guideline:
  • 1,000 cGy in 3 Fractions over 3 days, n=5
  • 1,320 cGy in 11 Fractions over 4 days, n=5
  • 1,200 cGy in 4 Fractions over 4 days, n=3

Results

• Median follow-up of 22 months (range of 7 - 44 mos)
• Grade 2-4 acute GVHD = 6 patients (46.2%)
• Grade 3-4 acute GVHD = 3 patients (25.0%)
• Chronic GVHD = 4 patients (33.3%, 2 limited, 2 extensive)
• Eleven patients are alive and event-free at median follow-up

Author's Conclusions

• Our results suggest that adding HDC to the standard cyclophosphamide/TBI conditioning  regimen is safe and feasible for allogeneic HSCT in childhood Ph+ ALL.
  
• This combination resulted in an excellent survival rate and acceptable toxicity, despite the fact that the majority of grafts were from an unrelated donor.

Clinical/Scientific Implications

• Although this is a small single-arm study and thus no control arm exists with which to compare the results, the data shown here are nonetheless very supportive of HDC. The authors document that the addition of HDC to the standard conditioning regimen is well-tolerated, especially in light of the large percentage of unrelated allogeneic donors in the study population.
• Furthermore, the fact that eleven of the 13 study patients are alive and free of relapse offers an extremely encouraging foundation on which to base both clinical change and implementation of this regimen as well as continued research in this area.