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  • HLA-haploidentical bone marrow transplantation  (1)
  • IL-4  (1)
  • Interferon  (1)
  • 1
    ISSN: 1432-1335
    Keywords: Osteosarcoma ; Preoperative chemo-therapy ; Limb salvage ; High dose methotrexate ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Fortyone patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin+cyclophosphamide+dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1–16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Key words Bone marrow stroma ; Myeloid leukemia ; TNF-α ; IL-4 ; Adhesion molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study the mechanisms of adhesion of myeloid leukemic cells to bone marrow stroma, we analyzed the interaction of bone marrow stromal fibroblasts with myeloid leukemic cell lines and the modulation of adhesion molecule expression on stromal fibroblasts by TNF-α and IL-4. Like others, we found up-regulation of VCAM-1 and ICAM-1 on fibroblasts with TNF-α treatment, whereby IL-4 acted synergistically with TNF-α. VCAM-1 expression on the cell surface was maximal after 10 h, while ICAM-1 expression increased up to 48 h. All myeloid leukemic cell lines tested (HL-60, K562, TMM, U937, ML-2, PLB-985, THP-1, KG1a) revealed weak adhesion to untreated bone marrow fibroblasts (≤10% bound cells). TNF-α and IL-4 significantly enhanced adhesiveness of fibroblasts to the cell lines PLB-985, THP-1, and ML-2, with a peak between 6 and 10 h of treatment. Adhesiveness to the cell line TMM was increased up to eightfold in a time-dependent manner for up to 48 h. The enhanced binding of ML-2-, THP-1-, and PLB-985 cells to stimulated fibroblasts was due at least partially to the interaction of VLA-4 with VCAM-1. Increased adhesion of TMM cells was impaired neither by antibodies to VLA-4, LFA-1, or Mac-1 nor by antibodies to their counter-receptors VCAM-1 or ICAM-1, suggesting that adhesion molecules distinct from VCAM-1 or ICAM-1 are involved in enhanced adhesiveness of the fibroblasts to myeloid leukemic cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1076
    Keywords: Adenosine deaminase deficiency ; HLA-haploidentical bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three infants with severe combined immunodeficiency and adenosine deaminase (ADA) deficiency were treated by T-cell depleted bone marrow transplantation (BMT), using human leukocyte antigen (HLA)-haploidentical parents as donors. In the first patient, two initial transplants failed to engraft and no change of the immunodeficiency was observed. In order to overcome this graft resistance, cytoreductive conditioning was used prior to a third transplant. In the other two patients, similar conditioning was used prior to initial transplants. In all three patients, complete and permanent immunological reconstitution was observed and they survive from 3.5 to 5 years after transplantation. In biopsies obtained from iliac bones prior to BMT, osteochondral abnormalities characteristic of ADA-deficiency were noted in all three patients. After successful transplantation, these abnormalities had completely resolved. Our results demonstrate that cytoreductive conditioning prior to HLA-haploidentical BMT is useful in order to obtain stable engraftment and reversal of abnormalities associated with ADA deficiency.
    Type of Medium: Electronic Resource
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