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Results of the "Mexican method" to conduct allogeneic hematopoietic stem cell transplantation

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 22 de marzo del 2007

Presenter: Ruiz-Argüelles, GJ
Presenter's Affiliation: Centro de Hematologia y Medicina Interna de Puebla, Mexico
Type of Session: Scientific

Background

• Myeloablative allogeneic bone marrow transplantation is used for several hematopoietic diseases, and is extremely expensive.  Non-myeloablative transplants, sometimes called “mini-allo” transplants, have been used in older patients with the goal of decreasing toxicity, but in North America, are still very expensive.
• Non-myeloablative transplants are being used for an increasing number of indications, including chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), relapsed Hodgkin’s disease and aplastic anemia.
• In 1999 a bone marrow transplantation program was started in México using a non-ablative conditioning regimen employing fludarabine, cyclophosphamide and busulfan. This was based on previously used regimens, but was aimed at decreasing the cost so it would be available a greater population of patients.
• This study was undertaken to assess the results of allografting individuals with different diseases using the "Mexican method" of allogeneic bone marrow transplantation.

Materials and Methods

• Retrospective, multi-institutional, multi-national study of results using the bone marrow transplant method described herein.
• Centers: Monterrey (México), Puebla (México), México City (México), Valencia (Venezuela), Sao Paulo (Brasil) and Medellín (Colombia)
• Patients - over 350 allografts in patients with a range of diseases:
  • Chronic myelogenous leukemia
  • Acute myelogenous leukemia
  • Acute lymphoblastic leukemia
  • Myelodysplasia
  • Thalassemia major
  • Relapsed Hodgkin´s disease
  • Blackfan-Diamond syndrome
  • Adrenoleukodystrophy
  • Hunter's syndrome
  • Aplastic anemia
  • Several solid tumors
• Treatment:  The "Mexican method" of allogeneic transplant:
  • oral busulphan, 4 mg / Kg on days - 6 and - 5
  • iv cyclophosphamide, 350 mg / m2 on days - 4, - 3 and – 2
  • iv fludarabine, 30 mg / m2 on days -4, -3 and -2
  • oral cyclosporin A, 5 mg / Kg starting on day – 1 until day + 180
  • iv methotrexate 5 mg / m 2 on days + 1, + 3, + 5 and + 11

Results

• Follow up: between 30 and 2000 days.
• Median granulocyte recovery time to 0.5 x 109/L: 13 days
• Median platelet recovery time to 20 x 109/L: 12 days
• Transfusion requirements:
  • one third of the patients did not need red blood cell transfusions
  • one third did not need platelet transfusions.
• The transplant was completed totally as an outpatient in > 70% of cases.
• There was graft failure in 8%, however since the preparative regimen is non-myeloablative, all these patents recovered endogenous hematopoiesis.
• GVHD: Acute: 50%; Chronic: 30%
• Median overall survival has not been reached.
  • 2000 day overall survival: 54%
  • 100-day mortality: 16%
  • Transplant-related mortality: 20%
• Median cost of each transplant was $18,000 USD
• The best results were obtained in CML and aplastic anemia, whereas the worse were obtained in lymphoblastic leukemia, with intermediate results for myeloblastic leukemia:
  • CML (n=21) (all stages): 750 day overall survival: 60%
  • CML (n=24) (first chronic phase): 830 day overall survival: 92%
  • AML (n=24): 860 day overall survival: 66%
  • ALL (n=19): 900 day overall survival: 22%
  • Aplastic anemia (n=23): 1500 day overall survival 91%
• HLA disparity: it is safe to conduct non-ablative allografting who have either an HLA identical (6/6) or compatible (5/6) sibling donor

Author's Conclusions

• The results using the "Mexican method" obtained initially in México have been reproduced in other Latin American countries.
• There is less toxicity overall and less frequency and severity of GVHD, and the efficacy is similar to myeloablative transplantation.
• The affordability of the procedure seems to be adequate, particularly for developing countries.

Clinical/Scientific Implications

• The authors provide a review of the extended use of the “Mexican method” of non-myeloablative bone marrow transplantation. Although the numbers are still small for each disease, the efficacy is generally comparable to myeloablative bone marrow regimens and the toxicity appears to be less.
• In developing countries, diseases that previously were only curable by myeloablative transplantation may be essentially incurable due to economic reasons. The development of an economic, safe, and effective procedure, such as the “Mexican method” is an important advance in worldwide public health.