A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia

Evidence suggests an advantage for TBI over BU as a component of conditioning regimens for allogeneic hematopoietic cell transplant in patients with ALL. We have employed both TBI and BU for conditioning in ALL and reviewed our experience to compare outcomes. From July 1989 to June 2008, we identified 86-adult ALL patients treated with either a TBI-or BU-based regimen and transplanted with either a well-matched sibling or unrelated donor. Data including demographics, immunophenotype, disease status and cytogenetic risk were examined by Cox proportional hazards analysis. Patients treated with TBI were older (median age 40 vs 33 years; P ¼ 0.018), had a higher-risk cytogenetic profile (P ¼ 0.010), were more often transplanted using an unrelated donor (P ¼ 0.038) and were treated more recently (Po0.001). There was a significant improvement in EFS (P ¼ 0.046), and a trend to improved OS (P ¼ 0.08) in patients treated with TBI compared with those treated with BU. However, the advantage for TBI could not be confirmed by multivariable analysis where only disease status retained statistical significance.

Section: Introductionmentioning

confidence: 99%

BU- vs TBI-based conditioning for adult patients with ALL

Kalaycio

Bolwell

Rybicki

et al. 2010

“…The use of TBI as a part of conditioning regimens for this type of treatment continues in the modern era, and appears to provide benefit over conditioning with chemotherapy alone in many settings [17][18][19][20] (Table 1). Although huge amounts of progress have been made with regard to optimal BMT methods in the past 50 years, myriad questions regarding technique and outcome remain.…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

Hill‐Kayser

Plastaras

Tochner

et al. 2010

TBI has been used widely in the setting of BMT over the past 3 decades. Early research demonstrated feasibility and efficacy in the myeloablative setting, in preparation first for allogenic BMT and later for autologous stem cell rescue. As experience with TBI increased, its dual roles of myeloablation and immunosuppression came to be recognized. Toxicity associated with myeloablative TBI remains significant, and this treatment is generally reserved for younger patients with excellent performance status. Reduced intensity conditioning regimens may be useful to provide immunosuppression for patients who are not candidates for myeloablative treatment. Efforts to reduce toxicity through protection of normal tissue using methods of normal tissue blocking and use of TLI, rather than TBI, continue. In the future, modalities such as helical tomotherapy, proton radiotherapy and radioimmunotherapy, may have roles in delivery of radiation to the BM and lymphoid structures with reduced normal tissue toxicity. With further investigation, these efforts may expand the therapeutic ratio associated with TBI, allowing safer delivery to a broader range of patients.

“…Bu/CP-based regimens have been reported in most studies to be as effective as a TBI-containing regimen for allograft recipients with acute leukemia and chronic myeloid leukemia (CML). [3][4][5][6] However, a randomized French study showed that TBI was better than Bu in patients undergoing BMT for AML. 7 A higher transplantation-related mortality occurred in patients with advanced disease on a Bu-containing regimen, compared to TBI in another randomized trial.…”

mentioning

confidence: 99%

The effect of busulphan on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite: time interval influence on therapeutic efficacy and therapy-related toxicity

Hassan¹,

Ljungman²,

Ringdén

et al. 2000

136

Summary:Busulphan and cyclophosphamide (Bu/CP) are widely used in preparative regimens for bone marrow transplantation. Many studies have shown a wide variation in busulphan pharmacokinetics. Moreover, higher rates of liver toxicity were reported in Bu/CP protocols than in a total body irradiation (TBI)-containing regimen. In the present paper we investigated the effect of the time interval between the last dose of busulphan and the first dose of cyclophosphamide on the pharmacokinetics of CP and its cytotoxic metabolite 4-hydroperoxycyclophosphamide (4-OHCP). Thirty-six patients undergoing bone marrow transplantation (BMT) were included in the study. We also investigated the occurrence of venoocclusive disease, mucositis and graft-versus-host disease. Ten patients conditioned with CP followed by TBI served as a control group (TBI). Twenty-six patients were conditioned with Bu/CP. The patients received Bu