Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic stem cell transplantation (SCT) is a highly effective therapy for childhood acute lymphoblastic leukaemia (ALL). Concerns about unnecessary toxicity and expense mean that SCT is currently largely reserved for children who cannot be cured with chemotherapy. Not surprisingly, many such children also fail SCT. Retrospective studies have shown that a single analysis of minimal residual disease (MRD) pre-SCT identified those at highest risk of relapse. It is now appropriate to call for the universal incorporation of standardized MRD testing into SCT protocols as the next step to maximize the clinical impact of this technology in ALL.
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PMID:Minimal residual disease prior to stem cell transplant for childhood acute lymphoblastic leukaemia. 1282 42

Reharvesting leukocytes from donors for a donor leukocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. It is well known that the effect of a growth factor-primed DLI is comparable to that of a nonprimed DLI. In total, 42 patients with hematologic malignancies and a high risk of relapse were allocated, on an intent-to-treat basis, a peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors, and then at the time of harvest, additional peripheral blood stem cells (PBSCs) were also reserved for a therapeutic primed DLI in case of relapse. In all, 12 patients who relapsed after allogeneic PBSCT were treated with mainly cytarabine-based chemotherapy followed by a cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLIs was 1.43 x 10(8)/kg and 4.75 x 10(6)/kg, respectively. Six of the 12 relapsed patients exhibited a complete response after the primed DLI, plus their 1-year survival rate was 33%. The new development or progression of graft-versus-host disease after a primed DLI was observed in 50% of the patients. Overall, the survival at 1 year was 16.7%. Accordingly, the induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the original time of harvest, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach is also more convenient for donors.
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PMID:A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant. 1464 58

St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 x 10(9)/L or more, or CNS-3 (5 or more leukocytes/microL with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lower-risk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% +/- 2.6% (SE); the 8-year rate was 78.6% +/- 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% +/- 0.8%, and that of isolated plus combined CNS relapse was 3.0% +/- 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% +/- 1.3% in the lower-risk patients who received a cumulative dose of 1.2 g/m(2) and 5.0% +/- 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m(2) (P = .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether.
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PMID:Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital. 1525 79

We retrospectively analyzed the prognostic significance of mixed chimerism and associated clinical parameters in 80 patients following unmanipulated allogenic stem cell transplantation. Chimerism studies were performed on marrow aspirates using fluorescent in situ hybridization and variable number tandem repeats techniques at day +30, day +90 and +12 months. The median overall survival (OS) was 24 months (range, 1-56 months). Mixed chimerism was found in 23, 28 and 14% of patients at day +30 (1 month), +90 (3 months), and +12 months, respectively. Day +30 chimerism studies failed to provide any prognostic information. Day +90 mixed chimeras (MC) had significantly higher relapse rates compared to day +90 complete chimeras (CC) at 6 months (P=0.03) and 18 months when compared to MC (P=0.03) following transplant. The median OS in day +90 MC and day+90 CC were, respectively (95% CI, 2-35 months), compared to 47 months (95% CI, 20-74 months) (P=0.02). In conclusion, chimerism studies on day +30 could be reserved for patients who fail to demonstrate engraftment. Day +90 MC had higher relapse rates and lower OS, and therefore may be considered for novel therapies and future studies.
Leukemia 2004 Oct
PMID:Mixed hematopoietic chimerism at day 90 following allogenic myeloablative stem cell transplantation is a predictor of relapse and survival. 1531 47

The management of CML has recently become increasingly complex. The Scotland Leukaemia Registry (SLR) sent questionnaires to all 26 Scottish haematology units, of which 18 (69%) responded. From January 1999 to December 2000, 64 new cases of CML were identified by the audit (incidence 0.64/100,00/yr), of which 46 were registered with the SLR. At diagnosis, all 18 units combined bone marrow examination with cytogenetics/FISH, but only 13 performed RT-PCR. Of four units that calculated the Hasford Score, only two used it to inform clinical decisions. 52% of patients entered clinical trials, 57% involving imatinib mesylate (IM). Of the 23 patients who were tissue typed, suitable donors were found for 18, 11 sibling, and 7 unrelated, representing 28% of the total patient population. Only 13/64 patients (20%) did not have a BMT donor identified or enter a clinical trial. Although 38% of units would consider reduced intensity allografting in patients > 60 years, no centres currently routinely tissue-type such patients. For first line therapy 56% of patients received hydroxyurea +/- interferon. Of the newer agents, 83% of units believed imatinib mesylate should be reserved for clinical trials, 83% would consider using oral ara-C and 89% pegylated-interferon.
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PMID:The Scotland Leukaemia Registry audit of incidence, diagnosis and clinical management of new patients with chronic myeloid leukaemia in 1999 and 2000. 1546 21

The clinical course of polycythaemia vera is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukaemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, with the drug of choice being hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2 V617F mutation in the vast majority of polycythaemia vera patients opens new avenues for the treatment of this disease. Novel therapeutic options theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib, affect JAK2 expression in some patients. Nevertheless, these drugs require further clinical experience and, for the time being, should be reserved for selected cases.
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PMID:The treatment of polycythaemia vera: an update in the JAK2 era. 1763 23

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) reveals very poor prognosis due to high incidence of relapse when treated with standard chemotherapy. Although >96% of patients with Ph+ALL achieved complete remission (CR) with imatinib-combined chemotherapy in a phase II clinical trial conducted by the Japan Adult Leukemia Study Group (JALSG), 26% of them experienced hematological relapse in a short time after achievement of CR. In this study, to establish a prediction system for risk of relapse, we analyzed gene expression profiles of 23 bone marrow samples from patients with Ph+ALL using cDNA microarray consisting of 27,648 cDNA sequences. Using the 19 randomly-selected test cases, we identified 16 genes that were expressed significantly differently between patients with (n=8) and without (n=11) continuous response; from the list of 16 genes, we selected the 6 'predictive' genes and constructed a numerical scoring system by which the two groups were clearly separated, with positive scores for the former and the negative scores for the latter. Scoring of 4 cases that were reserved from the original 23 cases predicted correctly their clinical responses. In addition, three cases whose BCR-Abl transcript levels failed to reduce sufficiently after induction therapy, also revealed negative scores. We also developed a quantitative reverse transcription-PCR-based prediction system that could be feasible for routine clinical use. Our results suggest that achievement of continuous response with imatinib-combined chemotherapy can be predicted by expression patterns in this set of genes, leading to achievement of 'personalized therapy' for treatment of this disease.
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PMID:Prediction of risk of disease recurrence by genome-wide cDNA microarray analysis in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy. 1761 87

This study was aimed to explore whether the GVHD in mice can be ameliorated and the GVL effect in mice can be reserved by transfusion of lymphocytes of donors fed with recipient splenocytes effect. Male (DBA-2) mice (H-2(d)) as donors were fed with BALB/c splenocytes, DBA-2 splenocytes, bovine serum albumin, or regular chow, every other day. Induction of tolerance was assessed by a mixed lymphocyte reaction (MLR). Female (BALB/c) mice (H-2(d)) as recipients received total body irradiation (TBI) of 6.0 Gy ((60)Cogamma-ray) followed by inoculation of 3 x 10(3) P388 mouse leukemia cells on the same day. Subsequently, tail vein injection of 2 x 10(7) splenocytes supplied by DBA-2 was undertaken. Control groups were fed identically without leukemia cell inoculation. The results showed that GVHD was significantly ameliorated and CD4(+)/CD8(+) ratio increased in recipient-mice transplanted with splenocytes of tolerated donors, compared with control animals. There was no significant difference in survival rate between different groups of recipients inoculated with leukemia cell. It is concluded that the peroral recipient-mouse splenocytes can ameliorate GVHD without hampering effect on GVL.
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PMID:[Effect of recipient mouse splenocytes taken orally by donor mouse on GVHD after splenocyte transplantation]. 1831 15

In 1997-2003, a protocol for treatment of acute myeloid leukaemia (AML) (except promyelocytic leukaemia) was activated in four Swedish health care regions covering 50% of the national population. Based on cytogenetics and clinical findings, patients aged 18-60 yr were assigned to one of three risk groups. In this report we account for the long-term clinical outcome of enrolled patients. Patients received idarubicin and cytarabine in standard doses as induction therapy and consolidation courses included high-dose cytarabine. Allogeneic stem cell transplantation (allo-SCT) from an human leucocyte antigen-identical sibling was recommended in standard and poor-risk patients, whereas unrelated donor transplant was reserved for poor-risk patients. Autologous (auto-SCT) was optional for standard or poor risk patients not eligible for allo-SCT. Two hundred seventy-nine patients with de novo or secondary (9%) AML, median age 51 (18-60) yr, corresponding to 77% of all patients in the population, were included. Twenty (7%) patients were assigned to the good risk group, whereas 150 (54%) and 109 patients (39%) were assigned to standard- and poor-risk groups, respectively. Induction failures accounted for 55 patients; 16 early deaths eight of whom had white blood cell (WBC) >100 at diagnosis, and 39 refractory disease. Thus, complete remission (CR) rate was 80%. At study closure, the median follow-up time of living patients was 90 months. Median survival time from diagnosis in the whole group was 27 months and 4-yr overall survival (OS) rate was 44%. In good, standard, and poor risk groups, 4-yr OS rates were 60, 57 and 24%, respectively. Median relapse-free survival (RFS) time in CR1 was 25 months and RFS at 4 yr was 44%. Four-year RFS rates were significantly (P < 0.001) different between the three risk groups; 64% in good risk, 51% in standard risk and 27% in poor risk patients. One hundred-ten transplantations were performed in CR1; 74 allo-SCT (50 sibling, 24 unrelated donor), and 36 auto-SCT. Non-relapse mortality was 16% for allo-SCT patients. Outcome after relapse was poor with median time to death 163 d and 4-yr survival rate 17%. Three conclusions were: (i) these data reflect treatment results in a minimally selected population-based cohort of adult AML patients <60 yr old; (ii) a risk-adapted therapy aiming at early allogeneic SCT in patients with a high risk of relapse is hampered by induction deaths, refractory disease, and early relapses; and (iii) high WBC count at diagnosis is confirmed as a strong risk factor for early death but not for relapse.
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PMID:Results of risk-adapted therapy in acute myeloid leukaemia. A long-term population-based follow-up study. 1938 87

Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.
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PMID:Large granular lymphocyte leukemia: natural history and response to treatment. 2036 69


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