Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a single centre experience of eight consecutive patients with relapsed or refractory Ph+ ALL treated with the FLAG/idarubicin regimen followed by BMT or PBSCT. Following FLAG/idarubicin, one achieved a partial response and seven CR. All patients subsequently received allogeneic transplants: one sibling BMT, three matched unrelated (MUD) BMT and four sibling PBSCT. Two patients received second transplants with PBSC from their original BM donors following FLA/Ida with no further conditioning. Three patients are alive in CR 9, 24 and 32 months after transplant. Seven of eight patients had a cytogenetic response following FLAG/Ida induction and one of seven became bcr-abl negative. All eight patients had a complete cytogenetic response following transplant. Four of five assessable patients became p190 bcr-abl negative after transplant; three of these subsequently relapsed. Both patients with the p210 bcr-abl transcript remained bcr-abl positive in CR after transplant. FLAG/Ida was well tolerated and appears to be effective in inducing remission in relapsed Ph+ ALL. The use of FDR-containing chemotherapy without further conditioning prior to PBSCT deserves further study in heavily pre-treated patients and, in patients with relapsed ALL following BMT, may be a safer option than DLI (donor lymphocyte infusion) by avoiding the associated risk of aplasia.
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PMID:FLAG-idarubicin and allogeneic stem cell transplantation for Ph-positive ALL beyond first remission. 989 15

Translocation t(9;22) or Philadelphia chromosome (Ph)/BCR-ABL rearrangement positive acute lymphoblastic leukemia (Ph/BCR+ ALL) is associated with a very short survival of about one year in most patients. We analyzed long-term outcome of 76 adults with Ph/BCR+ ALL, in order to detect which factors were associated with longer survival. Modifiable prognostic factors included type of treatment, allogeneic marrow transplant (allo-BMT), and early anthracycline dose intensity (high = H/A, low = L/A); unmodifiable factors were age, gender, FAB morphology, phenotype, blast count, P190/210 transcript, hepatospleno-lymphadenopathy, LDH level. Median patient age was 43 years (range 15-71). Four favorable prognostic factors (FPF) were found associated with greater likelihood of complete remission (blast count < 50 x 10(9)/l, p = 0.08), longer remission duration (age < 50 years, p < 0.001; H/A, p < 0.05), and lower relapse rate (allo-BMT, p = 0.017). Age and anthracycline dose intensity exerted a synergistic prognostic effect. According to the cumulative incidence of FPF in each patient (FPF 0-1 = 29, 2-3 = 42, 4 = 5), the probability of survival increased from nil to 0.22 to 0.60 at 5 years (p < 0.005). Adult Ph/BCR+ ALL is relatively sensitive to anthracyclines, which therefore should be prescribed at full dosage to patients not eligible to allo-BMT or in the waiting list for unrelated donor transplantation.
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PMID:Clinical sensitivity to anthracyclines in PH/BCR+ acute lymphoblastic leukemia. 1050 Aug 26

INK4A/ARF mutations are acquired in bcr/abl(+) lymphoid blast phase chronic myelogenous leukemia (CML) and bcr/abl(+) acute lymphoblastic leukemia (ALL). Donor lymphocyte infusion and graft-versus-leukemia (GVL) are generally ineffective in such ALLs, whereas GVL is highly active against bcr/abl(+) CML, which does not have a lesion in the INK4A/ARF locus. The mechanisms for the ineffectiveness of GVL are not fully known, and it is possible that intrinsic resistance of acute lymphoid leukemias to immune effectors associated with allogeneic GVL may contribute to ineffectiveness. This work tested the hypothesis that INK4A/ARF mutations that are associated with transformation of bcr/abl(+) CML to an ALL phenotype, and that are associated with increased resistance to apoptosis render ALL cells insensitive to allogeneic immune responses to minor histocompatibility antigens (mHA). Murine acute pre-B ALLs were induced by transfer of the human p210 bcr/abl gene into bone marrow of INK4A/ARF null mice. These ALL lines were then studied in a murine model of MHC-matched, mHA-mismatched allogeneic BMT. In vivo growth of these ALLs was inhibited in allogeneic transplants characterized by active allogeneic immune responses compared to their behavior in syngeneic transplants. In vitro ALLs with INK4A/ARF, p210 bcr/abl, or p190 bcr/abl mutations remained sensitive to anti-mHA cytolytic T cells. In addition, the ALLs were capable of inducing primary immune responses to mHAs in vivo. Thus, ALLs with INK4A/ARF or bcr/abl mutations are not intrinsically resistant to allogeneic T cell responses, suggesting that active immunotherapies against mHA have the potential to control such acute lymphoblastic leukemias.
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PMID:High-risk acute lymphoblastic leukemia cells with bcr-abl and INK4A/ARF mutations retain susceptibility to alloreactive T cells. 1848 87