Conditioning regimens for allogeneic bone marrow transplantation

Copelan, Edward A.

doi:10.1016/0268-960x(92)90019-m

Cited by 15 publications

(8 citation statements)

References 55 publications

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“…Several reports have compared different conditioning regimens. 21 Disease relapse has been a significant cause of failure after BMT using the standard CY/TBI regimen. 13,14,19 Therefore, intensification of the conditioning regimen has been investigated in multiple studies.…”

Section: Discussionmentioning

confidence: 99%

Addition of high-dose Ara-C to the BMT conditioning regimen reduces leukemia relapse without an increase in toxicity

Mineishi

Atkinson

et al. 1999

Bone Marrow Transplant

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Summary:The optimal conditioning regimen for allogeneic BMT for hematological malignancies is still to be determined. We used a conditioning regimen including high-dose Ara-C (HDAC)/CY/TBI for patients at high risk for leukemic relapse (regimen A, Ara-C 3 g/m 2 every 12 h for six doses followed by CY 45 mg/kg for 2 days and TBI 13.2 Gy in eight fractions) and a standard CY/TBI conditioning regimen for patients at low risk (regimen B, CY 60 mg/kg for 2 days and TBI 13.2 Gy in eight fractions). We analyzed 55 patients treated with regimen A (group A) and 36 patients with regimen B (group B). Relapse rates (10.9% in group A, 2.9% in group B, P = 0.23), 5-year overall (53.2% in group A and 60.8% in group B, P = 0.26) and disease-free (47.7% in group A and 60.8% in group B, P = 0.11) survival rates were not significantly different between these groups, although group A consisted of high-risk patients. Regimen-related toxicities were not significantly different between the two groups. This result suggests that adding HDAC to CY/TBI conditioning regimen may reduce leukemic relapse and improve survival without increasing regimen-related toxicities. Keywords: allogeneic BMT; conditioning; toxicity; Ara-C; relapse Allogeneic BMT has been used effectively to treat a variety of hematologic malignancies. 1 Particularly for CML or myelodysplastic syndromes (MDS), it represents the only curative treatment modality. The combination of high-dose CY and TBI has been considered as a standard conditioning regimen for allogeneic BMT. 2,3 A variety of different conditioning regimens are currently being used including those which contain high-dose Ara-C (HDAC) 4 or high-dose etoposide. 5 mens, 6-8 but no study so far has shown a significant advantage of other regimens over CY/TBI.At the University of Wisconsin-Madison, we have used the standard conditioning regimen of CY/TBI for patients at low risk for leukemic relapse after BMT, and an intensified conditioning regimen of HDAC/CY/TBI for patients at higher risk, based on the hypothesis that the increased antitumor activity of HDAC would decrease the expected high incidence of leukemic relapse in patients with poor prognostic factors. In this article we summarize a prospective comparison of results obtained with these two regimens. Patients and methodsAll patients who underwent matched related allogeneic bone marrow transplantation at the University of Wisconsin-Madison between February 1990 and March 1997 with the diagnosis of AML, ALL, CML or MDS were entered in this study. Patients were assigned to a regimen according to their risk for leukemic relapse after BMT. Patients with the following diagnosis were considered to be at higher risk for leukemic relapse:(1) AML/MDS: second or subsequent complete remission (CR); first or subsequent relapse; primary refractory AML; high-risk cytogenetic features including deletions of chromosome 5 or 7 (Ϫ5, Ϫ7) or multiple cytogenetic abnormalities; preceding MDS, persistent cytogenetic abnormalities, or with central nervous system (CNS) involve...

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Section: Discussionmentioning

confidence: 99%

Addition of high-dose Ara-C to the BMT conditioning regimen reduces leukemia relapse without an increase in toxicity

Mineishi

Atkinson

et al. 1999

Bone Marrow Transplant

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“…Indeed at low doses Cyclophosphamide inhibited the growth of murine hepatoma MH129 in immunocompetent but not in immunodepleted mice and the inhibition did not occur in mice given CD4+CD25+ T cells [166]. In this study the interesting observation was made that the administration of low dose Cyclophosphamide was more effective in causing depletion of CD4+CD25+ cells when given after tumor inoculation than when given before tumor inoculation: as the authors stated [166], this finding is of relevance to clinical Phenylalinine mustard + [147,[188][189][190][191] Busulfan + + [148,169,[192][193][194] Nitrosoureas + + [148,[195][196][197][198][199][200][201][202] Cis Platinum + + [170,203,204,205,[206][207][208][209][210][211][212][213][214][215] Difluoromethylornithine + + [280][281][282][283][284][285] trials of chemotherapy and immunotherapy combinations. In this study the interesting observation was made that the administration of low dose Cyclophosphamide was more effective in causing depletion of CD4+CD25+ cells when given after tumor inoculation than when given ...…”

Section: Anticancer Drugsmentioning

confidence: 81%

Anticancer Drug-Induced Immunomodulation and Cancer Therapeutics

Mihich

2007

CCTR

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In the light of increasing knowledge on the regulation of the efferent and afferent branches of antitumor immunity, on tumor-induced imbalances of immune response and on tumor escape mechanisms, it seem important to review the information available on the immunomodulating effects of anticancer drugs and their possible exploitation in cancer therapeutics.The immunomodulation induced by several antitumor antibiotics is considered with particular emphasis on the effects of Doxorubicin and their therapeutic exploitation. The immunomodulating effects of anticancer drugs considered include those of cyclophosphamide and other alkylating agents, of 6-mercaptopurine and other antimetabolities, of Vinca alkaloida, Taxanes, Thalidomide, Gleevec and Difluoromethyl ornithine. The positive effects on tumor immunity are discussed with reference to their potential exploitation in the therapeutics. The effects of certain anticancer drugs on tumor antigen expression are also discussed as a mechanism by which these agents increase tumor immunogenicity with consequent advantages for therapeutic exploitation and vaccine effectiveness. The need for increased molecular and clinical studies of anticancer drugs-induced immunomodulation is emphasized.

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“…Although the combination of BU and CYC has gained favor as a preparative regimen for allogeneic transplantation, it has limited efficacy for patients with advanced AML or MDS, and no other regimen has been reported as being superior for this group of patients [10,[27][28][29]. In our study, the dose of BU was reduced to minimize toxicity and a third alkylating agent, thiotepa, was added, with the goal of improving efficacy.…”

Section: Discussionmentioning

confidence: 99%

Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia

et al. 2001

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Sixty-two adults underwent marrow or blood stem cell transplantation from an HLAmatched related donor using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen for treatment of advanced myelodysplastic syndrome (MDS) (refractory anemia with excess blasts with or without transformation) or acute myelogenous leukemia (AML) past first remission. All evaluable patients engrafted and had complete donor chimerism. A grade 3-4 regimen-related toxicity occurred in eight (13%) patients, and a diagnosis of MDS was the only independent risk factor for grade 3-4 regimen-related toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19%. Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43% (95% CI, 28%-58%). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard ratio 10.8, P = 0.02). Three-year survival was 26% (95% CI, 14%-37%); survival rates were 29% for those transplanted for AML in second remission, 31% transplanted for AML in relapse, and 17% with MDS, and there were no independent risk factors for survival. TBC is an active preparative regimen for advanced AML. Patients with advanced MDS appeared to have a higher risk of toxicity and early mortality, and alternative preparative regimens should be considered for these patients. Am. J. Hematol. 67:227-233, 2001.

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Conditioning regimens for allogeneic bone marrow transplantation

Cited by 15 publications

References 55 publications

Addition of high-dose Ara-C to the BMT conditioning regimen reduces leukemia relapse without an increase in toxicity

Addition of high-dose Ara-C to the BMT conditioning regimen reduces leukemia relapse without an increase in toxicity

Anticancer Drug-Induced Immunomodulation and Cancer Therapeutics

Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia

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