Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara-C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted.
Leukemia 1989 Feb
PMID:Comparative trial of cytarabine and thioguanine in combination with amsacrine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol. 291 Dec 5

Eight new cases (five adults and three children) of acute leukemia characterized by the presence in bone marrow cells of a t(4;11)(q21;q23)and one similar case, a child, with a t(1;11)(p32;q23) are reported. All patients were diagnosed as having acute lymphoblastic leukemia (ALL) with high-risk features. Immunologically the blast cells of the nine cases showed a strikingly consistent immature lymphoid phenotype, i.e., TdT+, HLA-DR+, B4(CD19)+, CALLA(CD10)-, Smlg-, cmu-, BA-2(CD9)+ corresponding to a "null ALL." In addition, six of nine cases expressed the myeloid marker VIM-D5(CD15). By double immunofluorescence staining it was determined that the VIM-D5(CD15) antigen was expressed by terminal deoxynucleotidyl transferase-positive blast cells, excluding the possibility of double leukemia. In five cases investigation of the Ig heavy chain genes by Southern blot analysis showed clonal rearrangement of both Ig heavy chain gene alleles. These data suggest that the blast cells involved in t(4;11) leukemia represent early B-cell progenitors with "aberrant" expression of myelomonocytic features, possibly related to the 11q23 breakpoint.
Leukemia 1987 Jan
PMID:Characterization of the blast cells in acute leukemia with translocation (4;11): report of eight additional cases and of one case with a variant translocation. 311

A possible association between HLA antigens, susceptibility or resistance to leukemia, and responsiveness to treatment has been studied in 144 patients with childhood acute lymphoblastic leukemia (ALL) and compared to other prognostic factors, i.e. white blood cell (WBC) counts, age at onset, sex, ethnic origin, and cell surface markers. All sequentially newly diagnosed children (97) comprised the group for the prospective study (PSG) and were followed for 6 years. The group included 37 patients classified as T-ALL, 41 as CALLA+, 27 as NULL, 12 as B and pre-B, and 27 unclassified patients, who were diagnosed before 1980. During the follow-up period, 45 patients of the PSG died. Forty-seven patients designated long-term survivors (LTS) have been followed 6-20 years after diagnosis, having completed a 3-5 year course of anti-leukemia therapy, and having remained disease free thereafter. High WBC counts at diagnosis and T-cell-surface markers were associated with poor prognosis, as were enthnic origin and specific HLA antigens. Thus, there was one (1) a significant increase in HLA-A30 and a decrease in HLA B-14 in the PSG Jewish patients; and (2) a complete absence of HLA-ALL in LTS while, in the PSG, 8 of 9 HLA-All-positive patients died during the follow-up period. This suggests that HLA-All is associated with poor prognosis in childhood ALL.
Leukemia 1988 Dec
PMID:HLA-A11 is associated with poor prognosis in childhood acute lymphoblastic leukemia (ALL). 319 82

Fifty-eight pediatric patients with non-T acute lymphoblastic leukemia (ALL) were diagnosed and evaluated at the Sambur Center of Pediatric Hematology Oncology. At least six subtypes of non-T ALLs were identified, corresponding to the various stages of B-cell differentiation, by utilizing an extensive panel of monoclonal antibodies directed against T- B- and myeloid-cell differentiation antigens. Moreover, leukemic cells expressing the phenotype of early B cells could be driven to differentiate along the B- cell lineage to express CALLA and BL antigens and cytoplasmic and/or surface immunoglobulins (IgM). A unique phenotype of non-T ALL was also identified. These leukemic cells expressed B cell antigen exclusively, i.e., HLA/DR and B4 (CD19). Myeloid-cell antigens, however, were expressed on these cells spontaneously after a 24-hour incubation in culture medium in vitro. In addition, leukemic cells of four patients with a phenotype of HLA/DR, CD19, and CD10 expressed antigens of the T-cell lineage: CD7 (3AI) and CD2 (leu 5), and/or of the myeloid cell lineage (My7). These results provide confirming evidence for the wide scope of the heterogeneity of ALL. It stresses the validity of accurate classification of leukemia to identify biologically and clinically unique subtypes of ALL, which bears specific prognostic parameters; and designates therapeutic protocols.
Leukemia 1988 Dec
PMID:Heterogeneity of childhood acute lymphoblastic leukemia (ALL): monoclonal antibodies phenotyping and induction of differentiation in vitro. 326 67

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.
Leukemia 1988 May
PMID:Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation. 328 16

Twelve children with juvenile chronic myeloid leukemia (JCML) received chemotherapy or bone marrow transplants. The median survival of the patients treated with myelosuppressive agents was 19 months. These results demonstrate that intensive chemotherapeutic and supportive measures can prolong survival in JCML but do not affect ultimate outcome. Purported differentiation inducers--low dose ara-C and 13-cis-retinoic acid--were not effective in two patients. Two patients were prepared for bone marrow transplantation with standard antileukemic cytoreduction regimens; one died very early post-transplant, and the other had early reemergence of his disease. The third transplant patient underwent transplantation after his disease had entered an accelerated phase. He received a different immunosuppressive pretransplant regimen, but the leukemia recurred. The latter two patients initially engrafted with mismatched T cell-depleted marrow grafts, but had recurrence of the disease. Our data suggest that marrow transplantation is possible for JCML patients without HLA-identical donors, but for successful marrow transplantation different measures are necessary to eradicate the abnormal stem cell compartment.
Leukemia 1987 Oct
PMID:Juvenile chronic myeloid leukemia: therapeutic insights. 331 35

Two patients with acute nonlymphocytic leukemia (ANLL) (FAB-M4) and t(6;9)(p23;q34) are described. Immunological marker analysis revealed a phenotype of HLA-DR+/partly terminal deoxynucleotidyl transferase (TdT)+/CD13+ in both cases and CD33 positivity in one. The expression of CD13 and CD33 by TdT-positive cells was demonstrated by double immunofluorescence staining. Although it has been postulated that TdT plays a role in gene rearrangement, Southern blot analysis performed in one leukemia revealed that both the T cell receptor beta chain genes and the immunoglobulin heavy chain genes were in germ line configuration. Since we could not detect CD13+/TdT+ cells and CD33+/TdT+ cells in control bone marrow samples, double marker analysis was used to detect low numbers of residual leukemic cells during follow-up of one patient. A gradually increasing percentage of CD33+/TdT+ cells was detected in the bone marrow in a period of 6 months before hematological relapse. Although the t(6;9) may not be correlated to a specific French-American-British subtype, it may be associated with TdT-positive ANLL. Since TdT-positive ANLL seems to have a poor outcome, detection of TdT expression in ANLL patients is particularly important for diagnostic purposes. In addition, our results indicate that double immunological marker analysis for a myeloid marker and TdT allows detection of residual disease during follow-up.
Leukemia 1988 Mar
PMID:Translocation (6;9) may be associated with a specific TdT-positive immunological phenotype in ANLL. 334 92

Patients with hairy cell leukemia who responded to alpha-interferon (IFN-alpha) were compared to those who did not by examining their hairy cells throughout treatment. The examination of the cells by cytofluorography included the expression of surface antigens (such as B1, HLA, transferrin receptors, surface immunoglobulins, TAC), and cytofluorometric measurement of light scatter including forward (which correlates with cytoplasmic size and shape) and perpendicular (which correlates with nuclear size and shape) directions. Although the entire lymphocyte population from these patients was examined initially to look for changes in phenotype with treatment, in later studies an enriched leukemic population was examined and alterations in response to interferon treatment became more apparent. The monoclonal antibody M5 was used to enrich the hairy cell population via a panning technique. The enriched population contained greater than 90% tartrate-resistant acid phosphatase-positive hairy lymphocytes. By cytofluorographic analysis of these cells serially in four responding patients and one refractory, all of whom had been followed longer than 11 months, several observations were made: 1) leukemic cells from responding patients showed a rapid decline in the forward and perpendicular light scatter indicative of cell differentiation; 2) coexisting normal B cells showed no changes in the above features; and 3) leukemic cells exhibited a definite increase in the HLA antigen density and a slight decrease in transferrin receptors in responding patients but not in the refractory patient. The increase in HLA antigen expression by hairy cells indicates progression toward differentiation, and decrease in transferrin receptors correlates with growth reduction. These data indicate that the administration of IFN-alpha is associated with cellular changes toward differentiation. We can not exclude, however, the possibility of other actions of IFN-alpha in HCL as proposed by other investigators.
Leukemia 1987 Apr
PMID:Changes in hairy cells after alpha-interferon treatment as measured by flow cytometry. 366 51

By suppressing apoptosis, hemopoietic growth factors (HGFs) promote the survival of CD34+, HLA-DR+ marrow cells that are enriched for hemopoietic progenitor cells (HPC). In the present studies, we have examined the effects of pIXY321, a genetically engineered fusion protein of GM-CSF and IL-3 (GM-CSF/IL-3), on high-dose Ara-C (HIDAC) and taxol-induced apoptosis and survival of a multilineage HPC, the CFU-GEMM. Exposure to 1.0 mumol/l taxol for 24 h or HIDAC > or = 10 mumol/l for 4 h induced internucleosomal DNA fragmentation and the morphologic features of apoptosis in CD34+, HLA-DR+ cells. These treatments were associated with > or = 50% inhibition of the assayable CFU-GEMM colony numbers. Incubation in serum-free medium (SFM) alone for 24 h also induced apoptosis of CD34+, HLA-DR+ cells, which was associated with reduced intracellular levels of the bcl-2 gene product p26BCL-2. Co-treatment with pIXY321 (10 ng/ml) inhibited apoptosis of CD34+, HLA-DR+ cells incubated in SFM, without significantly increasing the intracellular p26BCL-2 levels. Furthermore, co-treatment with pIXY321 significantly reduced taxol- and Ara-C-induced apoptosis and promoted the survival of CFU-GEMM (P < 0.05). Taxol and Ara-C mediated apoptosis of CD34+, HLA-DR+ cells, and its inhibition by pIXY321, was not accompanied by any significant alteration in the intracellular p26BCL-2 levels. By demonstrating that co-treatment with pIXY321 confers significant protection against apoptosis of CD34+, HLA-DR+ cells as well as promotes survival of normal HPC exposed to clinically relevant schedules and concentrations of taxol of Ara-C, these results support the design of chemotherapy regimens incorporating pIXY321 plus taxol and/or high-dose Ara-C for solid tumors and/or acute leukemias. It is hoped that the use of such a cytokine might maintain normal HPC numbers following chemotherapy, therefore avoiding prolonged suppression.
Leukemia 1995 Nov
PMID:pIXY321 protects against Ara-C or taxol-induced apoptosis and loss of clonogenic survival of normal human bone marrow progenitor cells. 747 74

The bacterial superantigen staphylococcal enterotoxin A (SEA) is a highly potent activator of cytotoxic T cells when presented on MHC class II molecules of target cells. Our earlier studies showed that such SEA-directed T cells efficiently killed chronic B lymphocytic leukemia (B-CLL) cells. With the ultimate goal to replace the natural specificity of SEA for MHC class II molecules with the specificity of a monoclonal antibody (mAb), we initially made a mutated protein A-SEA (PA-SEAm) fusion protein with > 100-fold reduced binding affinity for MHC class II compared to native SEA. The fusion protein was successfully used to direct T cells to B-CLL cells coated with different B lineage specific (CD19, CD20) or associated (CD37, CD40) mAbs. The PA-SEAm protein was 10-100-fold more potent against mAb coated compared to uncoated HLA class II+ B-CLL cells. No correlation was seen between the amount of mAb bound to the cell surface and sensitivity to lysis. Preactivation of B-CLL cells by phorbol ester increased their sensitivity, and lysis was dependent on ICAM-1 molecules. However, no preactivation of the target cells was needed when a cocktail of two or four mAbs was used. Circulating leukemia and spleen cells were equally well killed. We conclude that the natural target specificity of SEA, MHC class II, can be reduced by mutagenesis and novel binding specificity can be introduced by linkage to tumor reactive mAbs. Our findings encourage the construction of recombinant SEA mutant fusion proteins for specific T cell therapy of hematopoietic tumors such as B-CLL.
Leukemia 1995 Sep
PMID:Antibodies are capable of directing superantigen-mediated T cell killing of chronic B lymphocytic leukemia cells. 754 52


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