title: Non-supralethal mitobronitol/cytarabine/cyclophosphamide conditioning without irradiation before bone marrow transplantation for accelerated chronic granulocytic leukemia: apparent absence of acute graft-versus-host disease.
abstract: Cytostatic chemotherapy instead of supralethal total body irradiation (TBI) has been increasingly used as an alternative myeloablative regimen before bone marrow transplantation (BMT). While irreversible azoospermia/amenorrhoea seems to occur less frequently with such conditioning, graft-versus-host disease (GVHD) remains unaffected. Five-year disease-free survival in accelerated chronic granulocytic leukemia (CGL), after BMT with matched sibling grafts has been 0.10-0.30. Mitobronitol, cytosine arabinoside, and cyclophosphamide were used for conditioning. Patients were transplanted with unmanipulated HLA/MLC identical sibling bone marrow. For recovery, a pathogen-low room was available without air filtering and laminar airflow. Seven of eight accelerated-CGL patients were engrafted: full allogeneic reconstitution was detected in four and mixed chimerism in three patients. Five out of the seven engrafted patients survived at least nine months (median = 42 months), two are considered cured (8-9 years survival). The four leukemia-free survivors displayed full allogeneic reconstitution and presented symptoms of chronic GVHD. One patient became a genetically verified father. Acute GVHD and veno-occlusive liver disease (VOLD) were absent in all patients, diffuse interstitial pneumonitis (IP) occurred in one case. Non-supralethal conditioning with mitobronitol/cytarabine/cyclophosphamide in accelerated-CGL allows allogeneic bone marrow reconstitution with survival and cure rates comparable to those achieved with other protocols using TBI or busulphan conditioning. Unlike the latter treatments, however, our protocol leads to fewer transplant-related complications including acute GVHD, IP, VOLD, and azoospermia/amenorrhoea.
authors.affiliation: First Department of Medicine, Semmelweis University Medical School, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Kelemen
authors.forename: K
authors.initials: K
authors.lastname: Jakab
authors.forename: G
authors.initials: G
authors.lastname: Váradi
authors.forename: M
authors.initials: M
authors.lastname: Jánossa
authors.forename: J
authors.initials: J
authors.lastname: Földi
authors.forename: R
authors.initials: R
authors.lastname: Dénes
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000601:surgery*; D008297:Male; D008927:Mitobronitol / Q000008:administration & dosage*; D009845:Oligospermia / Q000139:chemically induced
chemical_list: D003561:Cytarabine; D008927:Mitobronitol; D003520:Cyclophosphamide