Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia (ALL).

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 23 de marzo del 2007

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Presenter: Gómez-Almaguer, D
Presenter's Affiliation: Hospital Universitario de Nuevo León, Mexico
Type of Session: Scientific

Background

  • Adult acute lymphoblastic leukemia (ALL) is associated with a far worse prognosis than in the pediatric population.
  • Despite the optimal use of the antileukemic agents, reported cure rates range from 20-40% in high-risk ALL adult patients.
  • The use of hematopoietic stem cell transplantation (HSCT) is an option in these patients, and myeloablative regimens have been used. Non-myeloablative conditioning HSCTs (“mini-allo transplants”) are a less toxic alternative to the conventional and more toxic myeloablative radio-chemotherapy scheme.
  • Using the “Mexican method,” non-myeloablative conditioning HSCTs can often be performed as outpatients and at a much lower cost, allowing for HSCTs to be available in economically depressed regions.
  • There is very limited experience using non-myeloablative conditioning HSCT in ALL.
  • The goal of this study was to prospectively evaluate the use of non-myeloablative conditioning HSCT patients with high risk ALL patients in second remission.

Materials and Methods

  • Design: Phase II, multi-institutional, single arm prospective therapeutic trial in Mexico
  • Patients:
    • 43 ALL high-risk patients in second remission
    • Median age of the patients was 19 years
    • 19 females, 24 males
    • All had Karnofsky performance status 100%
  • Treatment: Allogeneic non-myeloablative conditioning HSCT
    • Donors: HLA-identical siblings
    • Conditioning:
      • oral busulphan 4 mg/Kg/2 days
      • i.v. cyclophosphamide 350 mg/m2/3 days
      • i.v. fludarabine 30 mg/m2/3 days
    • Immune suppression:
      • oral cyclosporin A 4 mg/Kg was started on day – 1
      • i.v. methotrexate 5 mg/m2 was delivered on days + 1, + 3, + 5 and + 11
  • Patients received a median of 5.0 x 106/ Kg CD34+ cells.
  • The procedure was carried out as an outpatient in 35 patients (81%)

Results

  • Engraftment:
    • Median time to reach 0.5 x 109/L granulocytes: 14 days
    • Median time to achieve above 20 x 109/L platelets: 15 days
  • Survival:
    • Thirteen patients (30%) are alive 1050 days (median follow-up 491 days) after the HSCT.
    • 100-day mortality was 25.5%.
    • Median survival: 200 days
    • Thirty patients died between day 47 and 1050 after the HSCT, most of them (70%) of an ALL relapse.
  • Graft versus Host Disease (GVHD):
    • Acute GVHD: Ten patients (23%)
    • Chronic GVHD: 8 patients (18.6%)
  • Twenty eight (65%) patients relapsed, 9 of whom had GVHD.

Author's Conclusions

  • Relapse remains the first cause of death in high-risk ALL patients.
  • Non-myeloablative HCST seems to have limited therapeutic effect in ALL patients with advanced disease.  
  • New ideas and emerging strategies should be employed in order to improve the outcome of these patients, like enhancement of graft-versus leukemia effects and the use HSCT in first complete remission.

Clinical/Scientific Implications

  • Although the “Mexican method” of non-myeloablative conditioning HSCT can be accomplished at a lower price and with less toxicity, the results in adult high-risk ALL continue to be poor with a 30% cure rate at 2 years. This is in a group that should have a somewhat better prognosis since the median age was 19 years. Of note, patients over the age of 15 are considered adults in this population. A direct comparison would be required to determine if myeloablative or non-myeloablative conditioning regimen are superior for adult ALL.
  • The authors state that they will continue to study non-myeloablative conditioning HSCT in adult patients with ALL, but may expand their studies to more favorable patients in their first remission.

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