Conferences   /   Conference and Meeting Announcements   /   2005   /   October

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

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.