Thiotepa, busulfan and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced chronic myelogenous leukemia.
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.
Przepiorka
D
D
Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, USA.
Khouri
I
I
Thall
P
P
Mehra
R
R
Lee
M S
MS
Ippoliti
C
C
Giralt
S
S
Gajewski
J
J
van Besien
K
K
Andersson
B
B
Körbling
M
M
Deisseroth
A B
AB
Champlin
R
R
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001752:Blast Crisis / Q000188:drug therapy / Q000628:therapy; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D012307:Risk Factors; D013852:Thiotepa / Q000008:administration & dosage* / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous
D018906:Antineoplastic Agents, Alkylating; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D003520:Cyclophosphamide; D013852:Thiotepa; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr; D002066:Busulfan