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To improve the prognosis of patients with metastatic or high-risk localized sarcoma in first CR, we explored the role of consolidation therapy with megatherapy and hematopoietic rescue. From 1986 to 1995, of 72 patients with Ewing’s sarcoma from three pediatric departments, 30 were diagnosed as high-risk patients. Of these 30 patients, six did not achieve complete remission and four refused megatherapy and received multimodal treatment (chemotherapy + surgery and/or radio- therapy). The remaining 20 patients received megatherapy. There were 15 males and five females with a median age of 10.8 years (range 2–18 years). Five patients had metastatic disease at initial diagnosis, nine patients had primary tumor in the pelvis and 13 had a tumor volume greater than 100 ml. Overall disease-free survival was 62.7 ± 11%; 40 ± 21.9% for those with metastatic disease, 76.2 ± 12.2% for those with tumor volume greater than 100 ml and 64.8 ± 16.5% for those with tumor in pelvic bones. In conclusion, megatherapy has improved the outcome of this group of patients relative to that expected following conventional therapy.

To evaluate cardiovascular toxicities associated with the infusion of cryopreserved grafts, we prospectively monitored the infusions of 29 autologous bone marrow transplant (BMT) recipients. Fifteen allogeneic BMT recipients served as a control group. Cardiac rhythm was recorded continuously with the Holter technique from at least 2 h before the start of graft infusion until 24 h after completion. Blood pressure was closely monitored during the same period. Graft infusions were performed through a standard transfusion filter with breaks between aliquots. When the infusion had commenced, diuretics were given frequently (40 and 40% of allogeneic BMT and autologous BMT recipients, respectively) to avoid fluid overload. Non-cardiovascular clinical toxicities were observed more frequently in autologous BMT patients (41% vs 6%, p = 0.02) and no significant differences were seen between autograft and allograft recipients in any of the measured cardiovascular parameters. The heart rate decreased slightly in both groups but no patient in either group had a heart rate of60 b.p.m. or heart block. No significant changes in blood pressure were detected in either group. Ventricular ectopic beats/atrial ectopic beats ratio increased in the autologous BMT group after graft infusion (0.7 vs 0, p = 0.1). Time to engraftment did not differ significantly from other published series. Our results suggest that increasing infusion time of cryopreserved material and using a standard filter may reduce toxicities associated with the infusion of cryopreserved grafts. Early administration of diuretics may contribute to better control of blood pressure.

Lymphocyte subset reconstitution was studied in 65 patients undergoing allogeneic and autologus bone marrow transplantation (BMT).The expression of molecules on the membrane of lymphocyte subsets was assessed by two-colour flow cytometry and a direct immunofluorescence assay. The functional capacity of the patient's T lymphocytes following transplantation was identified by stimulation whit peripheral blood lymphocytes; B cells from BMT recipients were tested for their ability to respond, in vitro, to pokeweed (PWD) mitogen.1) The proportion of CD8+ T lymphocytes was higher than the CD4+ T lymphocytes until 1 1/2 year after-BMT, with high percentage of immature T cells (CD3+, CD8+, HLA-DR+, CD25-) in the first nine months post-transplant. Moreover, a large proportion of T lymphocytes lacked CD5 expression in the first year following BMT. 2) T-cell proliferative response to PHA was low with subsequent recovery until normality. 3) Low numbers of B cells in the first two months with a significant increase since then until 1 1/2 year after-BMT; the phenotype of these B cells was mainly CD19+, CD5+. 4) High in vitro spontaneous immunoglobulin production by peripheral blood B lymphocytes and an impaired response to PWM was observed. 5) Increased percentage of cells with natural killer (CD56) cell phenotype was seen during the 2nd and 3rd months after the graft infusion. After 1 1/2 year postgrafting, this percentage returned to normal level.Taken together, these data indicate the existence of numerous abnormalities in several subsets of peripheral blood lymphocytes after BMT and suggest a slow kinetics of immune recovery after human marrow transplantation being complete between 18 and 24 months following BMT.