Allogenictransplantation of the bone marrow after regimens of lowintensity conditioning in therapy of patients with hemoblastoses

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Abstract

Aim. To investigate effectiveness of allogenic transplantation of the bone marrow (TBM) in the treatment
of hemoblastosis patients from a high risk group, the course of donor bone marrow retention, tolerance
and antitumor activity of this therapy.
Material and methods. 11 patients received TBM in low-intensity regimen in Hematological Research
Center in 1999-2001. All the patients were from a high risk group. Conditioning was based on the
combination of fludarabin with busulfan. The transplanted precursor cells were taken from the bone
marrow and/or peripheral donor blood. The retention was controlled by differential agglutination of
erythrocytes and amplification of hypervariable sites of DNA. Minimal residual disease was controlled
by standard cytogenetical tests, fluorescent in situ hybridization or reverse-transcriptase polymerase
chain reaction.
Results. All the patients tolerated pretransplantation conditioning well. By chimerism, signs of retention
of donor bone marrow on day +30 after TBM were observed in 9 patients of 11. Acute graft versus
host reaction developed in 5 patients. This reaction was treated conventionally with methylprednisone
and cyclosporin A, in 4 cases with a good effect. A complete remission persists in 5 patients. Mean follow-up
lasted for 241 days.
Conclusion. Thus, transplantation was successful in 50% patients with an unfavourable prognosis who
are still in a complete remission. This suggests efficacy of the above method of treatment.

References

  1. Rizzo J. D. New summary slides show current trends in BMT. ABMTR Newsletter 1998; 5 (1): 4-10.
  2. Barrett A. J. Mechanisms of graft-versus-leukemia reaction. Stem Cells 1997; 15:248-258.
  3. Giralt S., Eatey E., Korbling M. et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531-4536.
  4. Khouri I. F., Keating M., Korbling M. et al. Transplant-Lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancy. J. Clin. Oncol. 1998; 16: 2817-2824.
  5. Slavin S., Nagler A., Naparstek E. et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756-763.
  6. Carella A. M., Giralt S., Slavin S. Low intensity regimens with allogeneic hematopoietic stem cell transplantation as treatment of hematologic neoplasia. Haematologica 2000; 85: 304-313.
  7. Зотиков Е. А., Порешина Л. П., Кутьина Р. М. и др. Иммунологическая и гематологическая реконституция реципиента при трансплантации костного мозга от близкого родственника. Клин. лаб. диагн. 1997; I: 10-13.
  8. Кайдалова А. И., Смирнова О. В., Сурин В. Л и др. Оценка частоты встречаемости полиморфных аллелей локуса DXS52 Х-хромосомы человека в московской популяции. Генетика 1994; 30 (7): 966-968.
  9. Мисюрин А. В., Сурин В. Л., Соловьев Г. Я. Определение частоты встречаемости аллельных вариантов гена фактора фон Виллебрандта на основе полиморфизма числа тандемных повторов из 40-го интрона этого гена. Там же (5): 713-717.
  10. Boerwinkle E., Xiang W., Fourest E. et al. Rapid typing of tandemly repeated hypervariable loci by the PCR. Application to the apolipoprotein B3 HVR region. Proc. Natl. Acad. Sci. USA 1989; 86: 212-216.
  11. Horn G. Т., Richards В., Klinger K. V. Amplification of a highly polymorphic VNTR segment by the polymerase chain reaction. Nucleic Acids Res. 1989; 17 (5): 2140.
  12. Демидова И. А., Сурин В. Л., Менделеева Д. П. и др. Амплификация гипервариабельных участков генома для установления типа гемопоэза у больных гемобластозами после аллогенной трансплантации костного мозга. Генетика 1997; 33 (4): 546-549.
  13. Mitelman G., ed. ISCN (1995) Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Basel: S. Karger; 1995.
  14. van Dongen J. J. M., Macyntire E. A., Gabert J. A. et al. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of BIOMED-1 Concerted Action: Investigation of minimal residual disease in acute leukemia. Leukemia 1999; 13 (12): 1901-1928.
  15. Spitzer Т. R. Nonmyeloablative allogeneic stem cell transplant strategies and the role of mixed chimerism. Oncologist 2000; 5: 215-223.
  16. Carella A. M., Champlin R., Slavin S. et al. Mini-allografts: ongoing trials in s humans. Bone Marrow Transplant. 2000; 25: 345-350.
  17. Jatunen E., Myllykangas-Luosujarvi R. Stem cell transplantation for treatment of severe autoimmune diseases: current status and future perspectives. Ibid. 22: 351-356.
  18. Kapelushnik J., Or R., Slavin S. A fludarabine-based protocol for bone-marrow transplantation in Fanconi's anemia. Ibid. 1997; 20: 1109-1110.
  19. Spitzer T. R., McAfee S., Sackstein R. et al. Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematological malignancies. Biol. Blood Bone Marrow Transplant. 2000; 6: 309-320.
  20. Pelot M. R., Pearson D. A., Swenson K. et al. Lymphohematopoietic graft-versus-host reactions can be induced without graft-versus-host disease in murine mixed chimeras established with a cyclophosphomide-based nonmyeloablative conditioning regimen. Ibid. 1999; 5: 133-135.
  21. Childs R., Clave E., Contentin N. et al. Reduced toxicity and transplant-related mortality (TRM) following non-myeloablative allogeneic peripheral blood stem cell transplantation for malignant disease. Blood 1999; 94: 3234-3241.
  22. Storb R. Nonmyeloablative preparative regimens: experimental data and clinical practice. In: 55th Annual meeting: ASCO: Educational Book. 1999. 241.

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