Thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced chronic myelogenous leukemia

D. Przepiorka, I. Khouri, P. Thall, R. Mehra, M. S. Lee, C. Ippoliti, S. Giralt, J. Gajewski, K. Van Besien, B. Andersson, M. Körbling, A. B. Deisseroth, R. Champlin

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Abstract

Thirty-six adults with chronic myelogenous leukemia (CML) in second or greater chronic phase, accelerated phase, or blast crisis underwent marrow or blood stem cell transplantation from an HLA-matched sibling using high-dose thiotepa, busulfan and cyclophosphamide (TBC) as the preparative regimen. All evaluable patients engrafted and had complete donor chimerism. One patient failed to clear meningeal leukemia, and one patient had one of 30 metaphases positive for the Philadelphia chromosome at 2 months post transplant. The remainder of the patients studied had eradication of CML documented by cytogenetics and/or Southern blot for BCR gene rearrangement, and 13 of 15 patients studied became negative for the BCR gene rearrangement by polymerase chain reaction. Three-year relapse rate is 42% (95% CI, 19-64%). The relapse rate was significantly lower for patients transplanted without blast crisis (9% vs 100%, P <0.001). Eight (22%, 95% CI, 10-39%) patients had severe or fatal veno-occlusive disease (VOD). Elevated liver enzymes within 1 month prior to transplantation and transplantation using marrow were significantly associated with the occurrence of VOD. Three-year survival is 28% (95% CI, 13-43%). Survival was significantly higher for patients transplanted without blast crisis (45% vs 0%, P = 0.01). TBC is an effective preparative regimen for CML in accelerated phase but not refractory blast crisis, and it should be used with caution in patients with prior hepatopathy who have an increased risk of severe VOD.

Original languageEnglish (US)
Pages (from-to)977-981
Number of pages5
JournalBone Marrow Transplantation
Volume23
Issue number10
StatePublished - 1999
Externally publishedYes

Fingerprint

Thiotepa
Busulfan
Homologous Transplantation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cyclophosphamide
Blast Crisis
Gene Rearrangement
Transplantation
Bone Marrow
Recurrence
Philadelphia Chromosome
Chimerism
Chromosomes, Human, Pair 2
Survival
Stem Cell Transplantation
Metaphase
Southern Blotting
Cytogenetics
Siblings
Blood Cells

Keywords

  • Allogeneic bone marrow transplantation
  • Busulfan
  • Chronic myelogenous leukemia
  • Thiotepa

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Przepiorka, D., Khouri, I., Thall, P., Mehra, R., Lee, M. S., Ippoliti, C., ... Champlin, R. (1999). Thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced chronic myelogenous leukemia. Bone Marrow Transplantation, 23(10), 977-981.

Thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced chronic myelogenous leukemia. / Przepiorka, D.; Khouri, I.; Thall, P.; Mehra, R.; Lee, M. S.; Ippoliti, C.; Giralt, S.; Gajewski, J.; Van Besien, K.; Andersson, B.; Körbling, M.; Deisseroth, A. B.; Champlin, R.

In: Bone Marrow Transplantation, Vol. 23, No. 10, 1999, p. 977-981.

Research output: Contribution to journalArticle

Przepiorka, D, Khouri, I, Thall, P, Mehra, R, Lee, MS, Ippoliti, C, Giralt, S, Gajewski, J, Van Besien, K, Andersson, B, Körbling, M, Deisseroth, AB & Champlin, R 1999, 'Thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced chronic myelogenous leukemia', Bone Marrow Transplantation, vol. 23, no. 10, pp. 977-981.
Przepiorka, D. ; Khouri, I. ; Thall, P. ; Mehra, R. ; Lee, M. S. ; Ippoliti, C. ; Giralt, S. ; Gajewski, J. ; Van Besien, K. ; Andersson, B. ; Körbling, M. ; Deisseroth, A. B. ; Champlin, R. / Thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced chronic myelogenous leukemia. In: Bone Marrow Transplantation. 1999 ; Vol. 23, No. 10. pp. 977-981.
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abstract = "Thirty-six adults with chronic myelogenous leukemia (CML) in second or greater chronic phase, accelerated phase, or blast crisis underwent marrow or blood stem cell transplantation from an HLA-matched sibling using high-dose thiotepa, busulfan and cyclophosphamide (TBC) as the preparative regimen. All evaluable patients engrafted and had complete donor chimerism. One patient failed to clear meningeal leukemia, and one patient had one of 30 metaphases positive for the Philadelphia chromosome at 2 months post transplant. The remainder of the patients studied had eradication of CML documented by cytogenetics and/or Southern blot for BCR gene rearrangement, and 13 of 15 patients studied became negative for the BCR gene rearrangement by polymerase chain reaction. Three-year relapse rate is 42{\%} (95{\%} CI, 19-64{\%}). The relapse rate was significantly lower for patients transplanted without blast crisis (9{\%} vs 100{\%}, P <0.001). Eight (22{\%}, 95{\%} CI, 10-39{\%}) patients had severe or fatal veno-occlusive disease (VOD). Elevated liver enzymes within 1 month prior to transplantation and transplantation using marrow were significantly associated with the occurrence of VOD. Three-year survival is 28{\%} (95{\%} CI, 13-43{\%}). Survival was significantly higher for patients transplanted without blast crisis (45{\%} vs 0{\%}, P = 0.01). TBC is an effective preparative regimen for CML in accelerated phase but not refractory blast crisis, and it should be used with caution in patients with prior hepatopathy who have an increased risk of severe VOD.",
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AU - Przepiorka, D.

AU - Khouri, I.

AU - Thall, P.

AU - Mehra, R.

AU - Lee, M. S.

AU - Ippoliti, C.

AU - Giralt, S.

AU - Gajewski, J.

AU - Van Besien, K.

AU - Andersson, B.

AU - Körbling, M.

AU - Deisseroth, A. B.

AU - Champlin, R.

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N2 - Thirty-six adults with chronic myelogenous leukemia (CML) in second or greater chronic phase, accelerated phase, or blast crisis underwent marrow or blood stem cell transplantation from an HLA-matched sibling using high-dose thiotepa, busulfan and cyclophosphamide (TBC) as the preparative regimen. All evaluable patients engrafted and had complete donor chimerism. One patient failed to clear meningeal leukemia, and one patient had one of 30 metaphases positive for the Philadelphia chromosome at 2 months post transplant. The remainder of the patients studied had eradication of CML documented by cytogenetics and/or Southern blot for BCR gene rearrangement, and 13 of 15 patients studied became negative for the BCR gene rearrangement by polymerase chain reaction. Three-year relapse rate is 42% (95% CI, 19-64%). The relapse rate was significantly lower for patients transplanted without blast crisis (9% vs 100%, P <0.001). Eight (22%, 95% CI, 10-39%) patients had severe or fatal veno-occlusive disease (VOD). Elevated liver enzymes within 1 month prior to transplantation and transplantation using marrow were significantly associated with the occurrence of VOD. Three-year survival is 28% (95% CI, 13-43%). Survival was significantly higher for patients transplanted without blast crisis (45% vs 0%, P = 0.01). TBC is an effective preparative regimen for CML in accelerated phase but not refractory blast crisis, and it should be used with caution in patients with prior hepatopathy who have an increased risk of severe VOD.

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