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Conditioning Therapy (conditioning + therapy)

Distribution by Scientific Domains

Medical Sciences	71%

Selected Abstracts

Allogeneic haematopoietic cell transplantation for chronic myelogenous leukaemia in the era of imatinib: a retrospective multicentre study

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006
Martin Bornhäuser
Abstract:,Objective:,To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome-positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods:,We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling (n = 18) or unrelated (n = 43) donors after having been treated with IM. Forty-one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan (n = 25) or total-body irradiation (n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose-reduced conditioning with fludarabine-based regimens. Results:,The incidence of grades II,IV and III,IV graft-versus-host disease was 66% and 38% respectively. The probability of overall survival (OS), disease-free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non-relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine-based conditioning therapy, age ,40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion:,These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant-related mortality. [source]

Interstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignancies

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010
Benigno C. Valdez
Abstract Despite successful molecularly targeted, highly specific, therapies for hematologic malignancies, the DNA interstrand crosslinking agents, which are among the oldest and least specific cytotoxic drugs, still have an important role. This is particularly true in stem cell transplantation, where virtually every patient receives conditioning therapy with a DNA-alkylating agent-based program. However, due to concern about serious additive toxicities with combinations of different alkylating drugs, the last several years have seen nucleoside analogs, whose cytotoxic action follows vastly different molecular pathways, introduced in combination with alkylating agents. The mechanistic differences paired with different metabolic pathways for the respective drugs have clinically translated into increased safety without appreciable loss of antileukemic activity. In this report, we review pre-clinical evidence for synergistic antileukemic activity when nucleoside analog(s) and DNA-alkylating agent(s) are combined in the most appropriate manner(s), without a measurable decrease in clinical efficacy compared with the more established alkylating agent combinations. Data from our own laboratory using combinations of fludarabine, clofarabine, and busulfan as prototype representatives for these respective classes of cytotoxic agents are combined with information from other investigators to explain how the observed molecular events will result in greatly enhanced synergistic cytotoxicity. We further present possible mechanistic pathways for such desirable cytotoxic synergism. Finally, we propose how this information-backed hypothesis can be incorporated in the design of the next generation conditioning therapy programs in stem cell transplantation to optimize antileukemic efficacy while still safeguarding patient safety. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source]

Allogeneic haematopoietic cell transplantation for chronic myelogenous leukaemia in the era of imatinib: a retrospective multicentre study

Analysis of chimerism during the early period after allogeneic peripheral stem cell transplantation

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2001
B. Gleissner
As there are few reports on early evaluation of chimerism, we assessed fluorescence short tandem repeats (STR) by polymerase chain reaction (PCR) assays to analyse donor and recipient characteristics at early time points after peripheral stem cell transplantation (PBSCT). Peripheral blood of 13 patients was analysed in 1- to 2-day intervals starting from the day of PBSCT. Donor and recipient allelic patterns were determined by a commercially available multiplex STR assay that simultaneously evaluates four or five gene loci. Mixed chimerism appeared in all patients during days 1,9 after transplantation and preceded haematologic engraftment for 3,12 days. Even patients without myeloablative conditioning therapy (n=4) revealed donor allelic patterns within 1,5 days. Nine patients changed during the following days to a complete donor allelic pattern and had an uncomplicated post-transplant disease course. Four patients did not consistently retain complete donor chimerism; two of them relapsed within the next 3 months, one died from septicemia within 7 days, and the fourth, transplanted for aplastic anaemia, is still in complete remission. Overall, STR analysis using a simple and comparatively cheap multiplex system permits the detection of chimerism very early after transplantation and may provide relevant information that correlates with the clinical follow-up. [source]

Acute lymphocytic leukemia in adolescence with multiple osteolytic lesions and hypercalcemia mediated by lymphoblast-producing parathyroid hormone-related peptide: A case report and review of the literature

PEDIATRIC BLOOD & CANCER, Issue 3 2005
Hidemi Shimonodan MD
Abstract Background Osteopathy is one of the common initial symptoms of acute lymphocytic leukemia (ALL) in children and adolescents, but multiple osteolysis accompanied by hypercalcemia is rarely observed. Procedure We treated a 14-year-old female who had multiple osteolytic lesions and hypercalcemia at initial onset of ALL. In this case we examined some humoral factors, which are known to associate with hypercalcemia in malignancies. Results Parathyroid hormone-related peptide (PTHrP) was elevated in serum, and reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed that the lymphoblasts produced PTHrP directly. Other humoral factors related to hypercalcemia were not detected. ALL relapsed in the bone marrow 3 months after achieving complete remission, and hypercalcemia and elevation of serum PTHrP were also observed. A second remission could not be achieved and hypercalcemia continued. The patient received allogeneic bone marrow transplantation. The serum calcium level became normal after the conditioning therapy. Before engraftment, however, the patient died of infection. Conclusions The present case suggests that blast-producing PTHrP might be associated with multiple osteolytic lesions and hypercalcemia. PTHrP expressed in the lymphoblasts may, in itself, confer a survival advantage to lymphoblasts and contribute to the refractory nature of the disease. © 2005 Wiley-Liss, Inc. [source]

The role of pelvic traction in the management of primary monosymptomatic nocturnal enuresis

BJU INTERNATIONAL, Issue 4 2002
E.E.H. Hussein Mohamed
Objective To determine whether pelvic traction is beneficial in children with primary nocturnal enuresis. Patients and methods There can be disproportionate growth between the spinal column and neural tube in prepubertal children. The normal elongation of the vertebral column in children during sleep could stretch the filum terminale and nerve roots, representing a minor degree of tethering that affects neural function and contributes to nocturnal enuresis. Pelvic traction induces a similar or more intense stretch while a patient is fully awake (and able to control their bladder). Releasing the potential tethering in this way, combined with conditioning therapy, could be beneficial. Fifty patients (aged 7,17 years) with monosymptomatic primary nocturnal enuresis were evaluated in a prospective study. All had 10 sessions of pelvic traction applied over 4 weeks and were followed up for 3 months afterward; no other medications were given. Results All patients had fewer wet nights, with variable degrees of success (20,80%) during and 3 months after traction. Conclusion Pelvic traction is a safe, simple, economic and effective treatment for primary monosymptomatic nocturnal enuresis. [source]