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
Last Modified: March 23, 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.


News
Also, double unrelated cord blood transplant tied to better outcomes in leukemia patients

Dec 8, 2010 - Individuals who donate peripheral blood stem cells or bone marrow do not appear to be at an overall increased risk of cancer, according to research being presented at the annual meeting of the American Society of Hematology, held from Dec. 4 to 7 in Orlando, Fla. According to another study, acute myeloid or lymphoblastic leukemia patients who receive double unrelated cord blood transplants may experience better overall outcomes than those who receive single cord blood transplants. Other studies being presented address stem cell transplant procedures in treating various hematologic malignancies and highlight zoledronic acid's ability to improve survival in multiple myeloma patients.



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