Cyclophosphamide plus total body irradiation compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with leukemia: A systematic review and meta-analysis
ABSTRACT Cyclophosphamide plus total body irradiation (CYTBI) and oral busulfan plus cyclophosphamide (BUCY) are commonly used conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with leukemia. However, there is conflicting data on the superiority of one regimen over the other. Our aim was to critically appraise and synthesize available evidence regarding the efficacy and safety of CYTBI compared to BUCY as a conditioning regimen.
Systematic review and meta-analysis of randomized, controlled trials (RCTs) comparing BUCY with CYTBI.
We did a systematic search of the indexed medical literature using appropriate keywords to identify potentially relevant articles. The primary outcome of interest was efficacy measured by overall survival (OS) and disease-free survival (DFS). Acute and late toxicity were secondary endpoints. Meta-analysis was attempted only on RCTs. A relative risk or risk ratio (RR) and 95% confidence interval (CI) was calculated for each outcome in the meta-analysis.
Fifteen non-randomized comparative studies involving 6280 patients were included in a narrative review without attempting a pooled analysis, in view of the potential for significant bias. Outcome data from seven RCTs involving 730 patients randomly assigned to either CYTBI or BUCY was pooled using meta-analytic methods. CYTBI was associated with a modest but non-significant reduction in all cause mortality (RR=0.82, 95%CI: 0.64-1.05; P=.12) and relapse of leukemia (RR=0.89, 95%CI: 0.72-1.10; P=.28). Transplant-related mortality (TRM) was significantly lesser with CYTBI compared to oral BUCY (RR-0.53, 95%CI: 0.31-0.90; P=.02). The cumulative incidence of major complications was not significantly different between the two regimens, but specific complications varied according to the conditioning regimen. TBI-based regimens were associated with more severe late effects on growth and development in children.
This analysis represents the largest comparative analyses of CYTBI with BUCY as a conditioning regimen prior to HSCT in the indexed medical literature. Conditioning regimen and disease (type and setting) can significantly affect outcomes. TRM is significantly lesser with CYTBI, but this does not translate into a significant survival benefit. There remain valid concerns regarding the late effects of TBI, particularly in children. Although not overly superior, the weight of evidence favors CYTBI over BUCY as a first choice-conditioning regimen in patients with leukemia.
- SourceAvailable from: Cigdem Pala
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- "The goal from using TBI in the preparation regimens for BMT is threefold: destroying residual neoplastic cells, clearing the host marrow to allow repopulation with donor marrow cells, and providing sufficient immunosuppression to avoid allograft rejection by immunologically active cells in the host . Known adverse effects of TBI include nausea, vomiting , sweating and irritability as well as renal dysfunction, interstitial pneumonia, lung injury, cataract, osteosarcoma, and cystitis in rare cases       ; no case of acute transverse myelitis (ATM) has been reported. ATM is a neurological syndrome caused by inflammation of spinal cord, which may involve all age groups. "
ABSTRACT: Total body irradiation (TBI) combined with chemotherapy is widely used as a pretreatment regimen of bone marrow transplantation (BMT) in hematologic disorders. Late complications related to TBI as part of the conditioning regimen for hematopoietic stem cell transplantation have been revealed. Acute transverse myelitis (ATM) is a neurological syndrome characterized by disorder of motor, sensorial, and autonomic nerves, and tracts at medulla spinalis, which is resulted from involvement of spinal cord. In this paper, we presented an ATM attack developed after TBI in a patient with acute lymphoblastic leukemia (ALL) as it is a rarely seen case.07/2013; 2013:523901. DOI:10.1155/2013/523901
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- "In the medical application of therapeutic radiation , this is a measured induction of apoptosis and other cell death within a carefully defined volume. The impact of radiation on leukocytes can be viewed in similarly detrimental terms, whether attenuating lymphocyte numbers as tolerable side effect (Johnke et al., 2005; Lissoni et al., 2005) a therapeutic effect, such as part of an allogeneic transplant protocol (Wei et al., 2004; Gupta et al., 2011), or precipitating a secondary malignancy (Brill et al., 1962). The measurement of accumulated radiation injuries, such as micronuclei and DNA breakage in circulating lymphocytes, has been proposed as a direct assay of individuals' relative radiosensitivity (Minicucci et al., 2005; Tang et al., 2008; Ishihara et al., 2012); that sensitivity can be relevant to either toxicity or to treatment efficacy. "
ABSTRACT: Preclinical work in murine models suggests that local radiotherapy plus intratumoral syngeneic dendritic cells (DC) injection can mediate immunologic tumor eradication. Radiotherapy affects the immune response to cancer, besides the direct impact on the tumor cells, and other ways to coordinate immune modulation with radiotherapy have been explored. We review here the potential for immune-mediated anticancer activity of radiation on tumors. This can be mediated by differential antigen acquisition and presentation by DC, through changes of lymphocytes' activation, and changes of tumor susceptibility to immune clearance. Recent work has implemented the combination of external beam radiation therapy (EBRT) with intratumoral injection of DC. This included a pilot study of coordinated intraprostatic, autologous DC injection together with radiation therapy with five HLA-A2(+) subjects with high-risk, localized prostate cancer; the protocol used androgen suppression, EBRT (25 fractions, 45 Gy), DC injections after fractions 5, 15, and 25, and then interstitial radioactive implant. Another was a phase II trial using neo-adjuvant apoptosis-inducing EBRT plus intra-tumoral DC in soft tissue sarcoma, to test if this would increase immune activity toward soft tissue sarcoma associated antigens. In the future, radiation therapy approaches designed to optimize immune stimulation at the level of DC, lymphocytes, tumor and stroma effects could be evaluated specifically in clinical trials.Frontiers in Oncology 11/2012; 2:169. DOI:10.3389/fonc.2012.00169
Chapter: Cellular Therapy of ALLNovel Aspects in Acute Lymphoblastic Leukemia, 11/2011; , ISBN: 978-953-307-753-6