Combined resistance and aerobic exercise intervention improves fitness, insulin resistance and quality of life in survivors of childhood haemopoietic stem cell transplantation with total body irradiation.

PURPOSE: To investigate the effects of a supervised combined resistance and aerobic training programme on cardiorespiratory fitness, body composition, insulin resistance and quality of life (QoL) in survivors of childhood haematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI). PARTICIPANTS: HSCT/TBI survivors (n = 20; 8 females). Mean (range) for age at study and time since HSCT/TBI was 16.7 (10.9-24.5) and 8.4 (2.3-16.0) years, respectively. METHODS: After a 6-month run-in, participants undertook supervised 45- to 60-minute resistance and aerobic training twice weekly for 6 months, with a 6-month follow-up. The following assessments were made at 0, 6 (start of exercise programme), 12 (end of exercise programme) and 18 months: Body composition via dual energy X-ray absorptiometry, homeostatic model assessment of insulin resistance (HOMA-IR), cardiorespiratory fitness (treadmill-based peak rate of oxygen uptake (VO2 peak) test), QoL questionnaires (36-Item Short Form Health Survey (SF-36) and Minneapolis-Manchester Quality of Life Instrument (MMQL). RESULTS: Results expressed as mean (standard deviation) or geometric mean (range). There were significant improvements in VO2 peak (35.7 (8.9) vs 41.7 (16.1) mL/min/kg, P = 0.05), fasted plasma insulin (16.56 (1.48-72.8) vs 12.62 (1.04-54.97) mIU/L, P = 0.03) and HOMA-IR (3.65 (0.30-17.26) vs 2.72 (0.22-12.89), P = 0.02) after the exercise intervention. There were also significant improvements in the SF-36 QoL general health domain (69.7 (14.3) vs 72.7 (16.0), P = 0.001) and the MMQL school domain (69.1 (25.2) vs (79.3 (21.6), P = 0.03) during the exercise intervention. No significant changes were observed in percentage body fat, fat mass or lean mass. CONCLUSION: The supervised 6-month combined resistance and aerobic exercise programme significantly improved cardiorespiratory fitness, insulin resistance and QoL in childhood HSCT/TBI survivors, with no change in body composition, suggesting a metabolic training effect on muscle. These data support a role for targeted physical rehabilitation services in this group at high risk of diabetes and cardiovascular disease.

Stem cell source and outcome after hematopoietic stem cell transplantation (HSCT) in children and adolescents with acute leukemia.

Allogeneic hematopoietic stem cell transplantation from siblings, unrelated donors or HLA mismatched family members has become an important procedure to offer a chance of cure to children and adolescents with acute leukemia at high risk of relapse and those with certain genetic diseases. Bone marrow (BM) was the only stem cell source for many years. During the past 15 years, peripheral blood stem cells from granulocyte colony-stimulating factor (G-CSF) mobilized healthy donors, or umbilical cord blood from related or unrelated donors, have become available. Each stem cell source has different risks/benefits for patients and donors, the choice depending not only on availability, but also on HLA compatibility and urgency of the HSCT. This review will analyze the advantages and limitations of each of these options, and the main criteria which can be applied when choosing the appropriate stem cell source for pediatric transplant recipients with acute leukemia.

Haploidentical stem cell transplantation for children with acute leukaemia.

Some children with relapsed or high-risk acute leukaemia have an improved outcome if they have an allogeneic stem cell transplant, preferably from a sibling or well-matched unrelated donor. However, some children do not have these options or there is an urgent need to proceed to transplant because of disease status. We have investigated the role of haploidentical family members as donors in 34 patients with acute leukaemia (median age 11 years, range 1-16 years). Patients were conditioned with cyclophosphamide and total body irradiation (14.4 Gy in eight fractions) and received T-cell depleted peripheral blood stem cell grafts with a median CD34 cell dose of 13.8 x 10(6)/kg (range 4.2-35.1) and 0.7 x 10(4) CD3-positive cells/kg. The actuarial survival at 2 years was 26% (13-41%, 95% CI). Eight patients have survived disease-free with a median follow up of 62 months. They have good performance status and a median lymphocyte count of 1.8 x 10(9)/l. Relapse (14 patients) and adenoviral (six patients) or fungal infections (four patients) were the major causes of death. Haploidentical stem cell transplantation can produce medium term disease-free survival in a proportion of children with high-risk or relapsed acute leukaemia. None of the nine patients with acute myeloid leukaemia not in remission have survived.

Outcome of single fraction total body irradiation-conditioned stem cell transplantation in younger children with malignant disease--comparison with a busulphan-cyclophosphamide regimen.

The logistic difficulties of using fractionated total body irradiation (TBI) in the youngest children often limit the choice to single fraction TBI (sfTBI) or non-TBI-based regimens. We retrospectively evaluated 44 such children ( < 7 years) conditioned with either sfTBI (n = 26) or busulphan-cyclophosphamide (Bu-Cy) (n = 18), transplanted for hematological malignancies between 1988 and 2001. Both neutrophil and platelet engraftment were faster in the sfTBI group with a similar incidence of graft failure (6.8%). Acute GVHD (graft versus host disease) grade 2-4 occurred in 38.4% and 38.8% and chronic GVHD in 20% and 15.4% of the patients in the sfTBI and Bu-Cy groups, respectively Grade 2-4 GVHD was associated with reduced risk of relapse (p = 0.03). This finding was more pronounced in high-risk patients with 2/10 relapses in patients with GVHD grade 2-4, compared with 13/18 relapses among those with GVHD 0-1 (p = 0.05). The probability of overall survival was 43.3% in the sfTBI group and 33.3% in the Bu-Cy group (p = 0.6). However, the outcomes for high-risk patients and those with acute lymphoblastic leukemia were better in the sfTBI group. While hypothyroidism, growth hormone deficiency, learning problems and cataract formation were observed only in the sfTBI group, early cardiac toxicity, behavioral problems and seizures were more common in the Bu-Cy group. Thus, where fractionated TBI is not feasible, sfTBI offers improved survival in high-risk children with acute lymphoblastic leukemia compared with Bu-Cy, without an unacceptable increase in early or late toxicity.

The use of stimulated granulocyte transfusions to prevent recurrence of past severe infections after allogeneic stem cell transplantation.

The predictable neutropenia that follows allogeneic stem cell transplantation (ASCT) may be associated with recurrence of previous life-threatening infection. We describe nine patients with either previous invasive aspergillosis (IA) or considered to be at high risk of developing IA who underwent ASCT with prophylactic granulocyte transfusions. The study group, when compared with a control group, had a significant reduction in the incidence and duration of fevers (P < 0.05) and maximum C-reactive protein (P < 0.05). There were significantly fewer days of neutropenia (P < 0.05). There was also radiological improvement of pulmonary infiltrates in four out of seven assessable patients. No serious toxicity was encountered in donors or recipients. We conclude that prophylactic granulocyte donations can be given safely, and that they significantly reduce the number of days of neutropenia. Further investigation is warranted to determine whether granulocyte donations can prevent the recurrence of IA in patients at risk of fungal infection.