Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complement receptor type 1 is expressed by erythrocytes and most leukocytes. A soluble form is shed from the leukocytes and found in plasma (sCR1). sCR1 is a powerful inhibitor of complement. We report an increased sCR1 in the plasma of leukemia patients, up to levels producing measurable complement inhibition. Half of the 180 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) had sCR1 levels above the normal range. The highest levels were observed in T-ALL (17 patients). The complement function of a T-ALL serum was improved by blocking sCR1 with a specific mAb (3D9). Measurements in 16 peripheral stein cell donors before and after granulocyte colony-stimulating factor (G-CSF) administration showed an increase in sCR1 (before, 43.8+/-15.4; at day 5, 118.3+/-44.7 ng/mL; P < 0.0001). This increase paralleled the increase in total leukocyte counts and was concomitant with de novo leukocyte mRNA CR1 expression in all three individuals tested. Whether pharmacological intervention may be used to up-regulate sCR1 so as to inhibit complement in vivo should be further investigated.
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PMID:Soluble complement receptor 1 is increased in patients with leukemia and after administration of granulocyte colony-stimulating factor. 988 51

Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11 MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in 76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were calculated using the Kaplan-Meier product limit method. Variables potentially affecting survival and DFS were assessed in a multivariate analysis by the Cox proportional hazard model in a stepwise regression. The promising results were obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted after full dose induction and high dose consolidation was significantly longer if compared to those who received dose/time reduced or postponed treatment. For CR> or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage therapy that needs further improvement. In relapsed and refractory HD better results are obtained in patients relapsing > 1 year after first CR and in patients with entirely nodal localisation of this relapse. In NHL bone marrow and spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.
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PMID:Allogeneic and autologous bone marrow transplantation in single centre experience. 991 50

Haemopoietic cells from patients with acute myeloid leukaemia (AML) in first complete remission (CR1) show in vitro a haemopoietic defect and a decreased expansion potential. To better characterize this haemopoietic defect, CR1 AML and normal CD34+ cells were analysed for immunophenotype, viability, cell cycle and progenitor content before and during expansion culture in stroma-conditioned medium supplemented with cytokines. The production of haemopoiesis inhibitor by patient cells and the influence of high concentrations of stem cell factor (SCF) and Flt3-ligand (FL) on cell survival and ex vivo expansion potential were also studied. Before expansion, patient CD34+ cells showed viability and cell-cycle phase distribution similar to normal but lower percentages of CD34+DR- or CD34+CD38- cells and lower progenitor content. After 48 h of culture +/-30% of patient cells had died regardless of the cytokine combination used, whereas only 15% of normal cells died. After 7 d of culture, viability and cell cycle analyses showed comparable data for normal and patient samples. Co-culture of patient and normal cells did not show any evidence for haemopoiesis inhibitor production by patient cells. Even at high cytokine concentrations, a low progenitor expansion and a decrease in CD34+ cell numbers was observed for patient samples in contrast to normal samples. In conclusion, CR1 AML CD34+ cells showed excessive early cell mortality. No evidence for cell-cycle arrest or haemopoiesis inhibitor production was shown. SCF and FL used at high concentrations did not correct the patient cell expansion defect.
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PMID:In vitro evaluation of the haemopoietic defect of CD34+ cells from patients with acute myeloid leukaemia in first remission. 1044 77

Twenty-six patients affected by acute myeloid leukemia (AML) who relapsed after autologous stem cell transplantation (ASCT) were treated with the FLAG regimen (fludarabine, cytarabine, and G-CSF). Their median age was 39 years (range 14-59). The median interval from achievement of CR to ASCT was 4 months (2-8). The conditioning regimen was BAVC (BCNU, amsacrine, VP-16, cytarabine) in eight patients, BuCy (busulfan, cyclophosphamide) in 13, and TBI-Cy (total body irradiation, cyclophosphamide) in five. Relapse occurred after a median of 7 months (2-18). ASCT had been performed in CR1 for 23 patients and in CR2 for three. Nineteen patients had been given bone marrow, seven peripheral blood stem cells collected following consolidation plus G-CSF. Overall, CR was obtained by 13 patients (50%), all remitters requiring a single course. The median time for hematological recovery of neutrophils >500/microl and platelets >20,000/microl was 24 and 30 days, respectively. The median duration of G-CSF administration was 25 days, while the median hospitalization was 31 days. There were four deaths in induction (15%), while nine patients (35%) were resistant. After achieving CR, two patients received allogeneic BMT, five a second ASCT, and four were consolidated with HD-ARA-C. Only two patients were judged unable to receive any further therapy. There were 14 documented infections, while nine patients experienced fever of unknown origin. WHO >2 nonhematological toxicity consisted of stomatitis (50%), hepatic dysfunction (11%), diarrhea (11%), and lethargy (4%). Median overall survival and disease-free survival were 6 and 13 months, respectively. Six patients are in CCR at present. We conclude that FLAG is effective in patients with AML who are relapsing after ASCT. The toxicity is acceptable, enabling most patients to receive further treatment, including second transplantation procedures.
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PMID:Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of acute myeloid leukemia relapsing after autologous stem cell transplantation. 1046 Mar 53

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) for advanced acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in 383 adult patients in nine Australian adult BMT centres between 1981 and 1997. The median overall survival for the group was 4.8 months, with an estimated 5-year survival of 18%. 28% of patients died of transplant-related toxicities within the first 100 d. Progressive disease was responsible for 48% of deaths. Multi-factor analysis demonstrated that AML (v ALL), disease status (second complete remission [CR2] v others), age (< 40 years) and duration of prior first complete remission (CR1) (> 6 months) were pre-transplant variables significantly associated with improved survival. Acute graft-versus-host disease (GVHD) of any grade reduced the rate of relapse in both AML and ALL, but only grades I-II were associated with improved survival. Both limited and extensive chronic GVHD were associated with increased survival. Only patients with AML in untreated first relapse or CR2, with a duration of CR1 > 6 months, or patients with T ALL, had a 5-year survival > 20%. Transplants for AML in induction failure or pre-B ALL in untreated first relapse or CR2 had an intermediate outcome, with 5-year survival of 10-20%. A 5-year survival of < 10% was observed for patients transplanted for ALL in induction failure or for pre-B ALL or AML in refractory first relapse or beyond CR2. These results suggest that for most adult patients with advanced acute leukaemia an allograft offers only a small chance of cure.
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PMID:Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia. 1058 35

Several prospective randomized trials in acute myelocytic leukemia (AML) documented a lower relapse rate with autologous bone marrow transplantation (ABMT) than with conventional chemotherapy. However, they also identified some transplant difficulties, such as failure to collect sufficient numbers of stem cells, slow kinetics of engraftment, and a high transplant-related mortality that diminished or negated positive impact on overall survival. Data for ABMT are inconclusive in acute lymphocytic leukemia (ALL) in adults. We retrospectively analyzed patients with acute leukemia autografted with marrow purged with mafosfamide after January 1983 in our institution. The population comprised 229 consecutive patients; 165 with AML [123 in first remission (CR1), 32 in second remission (CR2)]; 61 with ALL (46 in CR1, 4 in CR2); and 3 with undifferentiated acute leukemia. All patients were autografted with marrow purged with mafosfamide. Mafosfamide was given at a constant dose of 50 microg/mL in 103 and adjusted individually to produce a CFU-GM LD 95 (5% residual CFU-GM post purging) in 126. The outcome was analyzed for correlation with patient characteristics, the disease including cytogenetics, and the graft itself. Prognostic factors identified by multivariate analysis were used to derive a prognostic classification. Patients receiving higher doses of marrow submitted to purging (>5.46 x 10(4) CFU-GM/kg) experienced a lower treatment-related mortality (RR = 0.11, p = 0.005) and a higher leukemia-free (RR = 0.5, p = 0.005) and overall survival (RR = 0.4, p = 0.001). Patients receiving <0.004% CFU-GM of marrow actually infused post purging had a lower relapse rate (RR = 0.51, p = 0.003). Modeling of prognostic groups identified good-, intermediate-, and poor-risk categories. Patients receiving a stem cell dose evaluated before purging of >5.46 x 10(4) CFU-GM/kg and doses actually infused post purging of < or =0.02 x 10(4)/kg had a treatment-related mortality of only 2+/-2%, a leukemia-free survival of 70%, and an overall survival of 77+/-7% at 10 years. In this study of autotransplantation for acute leukemia using mafosfamide-purged marrow, the stem cell dose used for purging and the intensity of purging were the most important factors predicting outcome.
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PMID:Importance of marrow dose on posttransplant outcome in acute leukemia: models derived from patients autografted with mafosfamide-purged marrow at a single institution. 1064

We have compared the outcomes of 87 patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) receiving matched sibling transplants with stem cells from peripheral blood (blood cell transplant, BCT) or bone marrow (BMT). In good risk patients (AML in CR1) granulocytes recovered to 0.5 x 10(9)/l a median of 14 days after BCT compared with 19 days after BMT (P < 0.0001). For patients with poor risk disease (AML beyond CR1 and MDS) corresponding figures were 16 vs 26 days (P < 0.0001). Platelet recovery to 20 x 10(9)/l was also faster after BCT (good risk 12 vs 20 days, P < 0.0001; poor risk 17 vs 22 days, P = 0.04). Red cell transfusions were unaffected by cell source, but BCT recipients required less platelet transfusions (good risk 1 vs 5, P = 0.002; poor risk 5 vs 11, P = 0.004). Blood cell transplants resulted in more chronic GVHD (86% vs 48%, P = 0.005) and a significantly higher proportion of recipients with KPS of 80% or less (48% vs 5%, P = 0.004). Disease-free survival at 4 years was 23% for both groups of poor risk patients but outcome in good risk patients was better after BCT (93% vs 62%, P = 0.047) related mainly to less relapse. While disease-free survival may be better after BCT than BMT for AML in CR1, quality of life may be relatively impaired.
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PMID:Allogeneic blood stem cell and bone marrow transplantation for acute myelogenous leukemia and myelodysplasia: influence of stem cell source on outcome. 1064 5

Host cells are protected from the lytic effect of the complement system by complement regulatory proteins. This study was designed to investigate the expression of complement regulatory proteins on leukemic blasts which may be susceptible to the lytic effects of the complement system in the circulation. The surface expressions of complement regulatory proteins, complement receptor 1 (CR1, CD35), decay accelerating factor (DAF, CD55), and homologous restriction factor 20 (HRF20, CD59), on peripheral blood and bone marrow blasts were evaluated by using flow cytometry in 16 acute myeloblastic leukemia (AML), 16 acute lymphoblastic leukemia (ALL), 4 chronic lymphocytic leukemia (CLL), 3 chronic myelocytic leukemia (CML) patients and control granulocytes and lymphocytes obtained from 15 healthy volunteers. mRNA expression was investigated by Northern blot analysis. mRNA abundances were calculated after normalization according to 28s rRNA. Surface expressions of CRI and DAF were marginally (p = 0.08 and p = 0.08, respectively) lower in AML, and DAF expression was significantly lower (p=0.0008) in ALL patients in comparison to their normal counterparts. Except from a slight increase that is detected for CD59 in CML patients (p=0.06), there was no significant difference between the surface expressions of CD59 in any of the groups studied. Densitometric analysis of autoradiographs obtained from Northern blots revealed that in AML patients, CR1 mRNA expression were 5.5-fold lower than controls (p=0.06), while DAF mRNA expression was significantly higher (p=0.0046). Furthermore, the mRNA expression of CRI in ALL patients was found significantly lower than in the control group (p = 0.0419). None of the values obtained from the other groups were significantly different from each other. These results suggest that leukemic blasts are protected from the lytic attack of the complement system at all levels, since all of the complement membrane regulatory proteins were expressed in all leukemia types (although at lower amounts in some cases), and it is also possible to use CRI and DAF as differentiation markers in acute leukemias.
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PMID:Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. 1068 Jul

Immunological control of acute leukemia may be achieved after allogeneic transplant. Despite promising preliminary results, the impact of immunotherapy with interleukin-2 (r-IL-2) on patients with acute leukemia (AL), in first complete remission (CR1) remains unclear. We conducted a prospective multicenter randomized trial to compare outcome in patients with AL in CR1, treated with autologous bone marrow transplantation (BMT) with or without postgraft r-IL-2. One hundred and thirty patients with AL in CR1 (myeloblastic (AML): N = 78; lymphoblastic (ALL): N = 52) were randomized at time of BMT to receive (N = 65) or not (N = 65) r-IL-2. r-IL-2 (RU 49637 from Roussel Uclaf) was started after hematological recovery, as a five cycle regimen (12 M IU/m2/day continuous infusion on day 1-5, 15-17, 29-31,43-45 and 57-59). The two groups were balanced for patient and transplant characteristics. Analysis was based on an intent to treat. Thirty-eight (59%) of the 65 patients randomized into the study group started r-IL-2 at a median of sixty-eight days (23-140) after transplant and received 77% (16-100) of the scheduled dosage. They received a median of 120 x 10(6) IU/m2 (25-156) over 10 (3-13) days during a total median period of 56 (3-78) days. With a median follow-up of 7 years (5.4-8.1 years), 79 patients relapsed (study group: 43 (66%); control group: 36 (55%): p = NS). Survival and leukemia-free survival estimates were 33% (23-45) versus 43% (22-52) and 29% (19-41) versus 36% (24-51) respectively for study and control groups (all p = NS). These results show that leukemic control after autologous BMT is not increased by r-IL-2 therapy. Further studies should investigate more appropriate r-IL-2 schedules and the possibilities offered by better antigen recognition and activated effector cells.
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PMID:Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission. 1070 5

One hundred and thirty-eight patients with AML underwent ABMT with monoclonal antibody plus complement-purged marrow between August 1984 and March 1997. One hundred and ten patients were in CR (CR1: 23; CR2/3: 87) and 28 were in first relapse (R1) at ABMT. Preparative regimens included busulfan (16 mg/kg) and CY (120 mg/kg) (n = 93), CY (120 mg/kg over 2 days) with TBI (1200 cGy) (n = 35), and busulfan (16 mg/kg) plus etoposide (60 mg/kg) (n = 10). CR1 patients treated with CY/TBI (n = 7) had 3- and 5-year disease-free survival (DFS) rates of 71% and 57%. CR1 patients treated with BU/CY (n = 12), had 3- and 5-year DFS rates of 45%. Three and 5-year DFS for CR2/3 patients treated with CY/TBI (n = 26) was 23%. Three- and 5-year DFS for patients in CR2/3 treated with BU/CY (n = 55) was 31 and 28%. Three- and 5-year DFS for patients in R1 treated with BU/CY (n = 26) was 37%. In multivariate analysis, increased age was associated with greater risk of death and relapse. For CR2/3 patients, the length of CR1 was a significant predictor of DFS. ABMT performed in CR or R1 results in excellent 5-year DFS and OS. The contribution of purging may require a randomized trial comparing purged vs unpurged stem cell infusions.
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PMID:Autologous bone marrow transplantation for acute myeloid leukemia in remission or first relapse using monoclonal antibody-purged marrow: results of phase II studies with long-term follow-up. 1080 2


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