Amifostine (WR2721) for dose escalation in marrow-ablative treatment of leukaemia

Martens, Anton C.; Hagenbeek, Anton

doi:10.1016/s0959-8049(98)00412-2

Cited by 7 publications

(4 citation statements)

References 32 publications

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“…In nonleukemic rats, 0/8 survived without amifostine, but 6/8 survived with amifostine. In leukemic rats only 11/36 rats survived if untreated, but 25/36 survived if pretreated with amifostine [153].…”

Section: Exogenous Agentsmentioning

confidence: 98%

Bone marrow stem cell protection from chemotherapy by low–molecular-weight compounds

Guest

Uetrecht

2001

Experimental Hematology

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Section: Exogenous Agentsmentioning

confidence: 98%

Bone marrow stem cell protection from chemotherapy by low–molecular-weight compounds

Guest

Uetrecht

2001

Experimental Hematology

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“…185,186 The BNML rat model has also been evaluated in appraising therapeutic index, optimisation of dose schedules and combinations of anthracyclines, [187][188][189][190][191][192][193] Ara-C, 158,[194][195][196][197][198][199][200][201][202][203][204][205][206][207][208] AMSA 209 and several other therapeutics. [210][211][212][213][214][215][216][217][218][219][220] The concern of relapse following autologous bone marrow transplant (ABMT) in human AML was initially addressed in the BNML rat model, examining antileukemic effects as well as toxicity of various conditioning regimes prior to ABMT, 221,222 including total body irradiation (TBI), 223 marrow ablative chemoradiotherapy, [224][225][226][227][228][229]...…”

Section: Transplantable Modelsmentioning

confidence: 99%

Animal models of acute myelogenous leukaemia – development, application and future perspectives

2005

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From the early inception of the transplant models through to contemporary genetic and xenograft models, evolution of murine leukaemic model systems have been critical to our general comprehension and treatment of cancer, and, more specifically, disease states such as acute myelogenous leukaemia (AML). However, even with modern advances in therapeutics and molecular diagnostics, the majority of AML patients die from their disease. Thus, in the absence of definitive in vitro models which precisely recapitulate the in vivo setting of human AMLs and failure of significant numbers of new drugs late in clinical trials, it is essential that murine AML models are developed to exploit more specific, targeted therapeutics. While various model systems are described and discussed in the literature from initial transplant models such as BNML and spontaneous murine leukaemia virus models, to the more definitive genetic and clinically significant NOD/SCID xenograft models, there exists no single compendium which directly assesses, reviews or compares the relevance of these models. Thus, the function of this article is to provide clinicians and experimentalists a chronological, comprehensive appraisal of all AML model systems, critical discussion on the elucidation of their roles in our understanding of AML and consideration to their efficacy in the development of AML chemotherapeutics.

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“…Because relapse is also a major cause of poor outcome for patients who undergo intensive conditioning, it is not realistic to expect fewer relapses with reduced-intensity conditioning unless other mechanisms of enhancing an antitumor effect are developed. Strategies that protect against regimen-related toxicity, such as amifostine [21], may permit more intense regimens for this group of patients. Another approach is the use of DLIs to prevent relapse.…”

Section: Reduced-intensity Conditioning Did Not Cure Most Patients Wi...mentioning

confidence: 99%

Lowered-intensity preparative regimen for allogeneic stem cell transplantation delays acute graft-versus-host disease but does not improve outcome for advanced hematologic malignancy

Levine¹,

Uberti²,

Ayash³

et al. 2003

Biology of Blood and Marrow Transplantation

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Reduced conditioning intensity has extended the option of allogeneic hematopoietic stem cell transplantation to patients who cannot tolerate fully myeloablative regimens. However, relapse and graft-versus-host disease (GVHD) continue to be major causes of morbidity and mortality. We prospectively tested whether a moderate reduction of the intensity of the preparative regimen would lead to significant reduction in regimen-related toxicity without compromising tumor control in a cohort of 44 patients ineligible for conventional hematopoietic stem cell transplantation. Patients were conditioned with fludarabine, busulfan, mycophenolate, and total lymphoid irradiation. Tacrolimus and methotrexate were given as prophylaxis for GVHD. Donors were 5 of 6 or 6 of 6 matched family members. The median age was 61 years. Eleven patients had comorbid conditions that precluded conventional myeloablative transplantation. Fatal regimen-related organ toxicity occurred in 3 patients. The cumulative incidence of grade 2 to 4 or grade 3 to 4 acute GVHD by day 100 was 38% (95% confidence interval [CI] = 25%, 55%) and 20% (95% CI = 10%, 39%), respectively, with a median time to onset of 66 days. For the entire cohort, 1-year overall survival, disease-free survival, and relapse rates were 54% (95% CI = 41%, 71%), 47% (95% CI = 35%, 65%), and 37% (95% CI = 19%, 51%), respectively. Outcomes differed based on stage of disease at time of transplantation, advanced (n = 19) versus nonadvanced (n = 25). Median survival times were 138 days and 685 days for subjects with advanced and nonadvanced disease, respectively (P =.005). After adjusting for age and comorbidity, disease stage continued to be significantly associated with overall survival (P =.005). In conclusion, a moderate reduction in conditioning dose intensity resulted in delayed onset of acute GVHD (compared with historical controls). A reduction in conditioning intensity is associated with poor survival for patients with advanced-stage disease, highlighting the importance of the conditioning regimen for tumor control.

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Amifostine (WR2721) for dose escalation in marrow-ablative treatment of leukaemia

Cited by 7 publications

References 32 publications

Bone marrow stem cell protection from chemotherapy by low–molecular-weight compounds

Bone marrow stem cell protection from chemotherapy by low–molecular-weight compounds

Animal models of acute myelogenous leukaemia – development, application and future perspectives

Lowered-intensity preparative regimen for allogeneic stem cell transplantation delays acute graft-versus-host disease but does not improve outcome for advanced hematologic malignancy

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