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PubMed1997

Characterization of a t(10;12)(q24;p13) in a case of CML in transformation.

We have used Southern blotting and fluorescence in situ hybridization (FISH) to define the breakpoints of a reciprocal translocation, t(10;12)(q24;p13), acquired as a secondary abnormality in a patient with Philadelphia chromosome positive chronic myeloid leukemia (CML) in transformation. A YAC clone that spanned the breakpoint at 12p13 was identified; this YAC included the CDKN1B gene but did not include ETV6. Neither ETV6 nor CDKN1B was rearranged, as determined by FISH and Southern blotting; however, a small deletion encompassing the translocated CDKN1B allele was detected. Analysis of two candidate genes at 10q24, HOX11 and NFKB2 suggested that they are not involved in this translocation. The preliminary mapping of breakpoints in this case demonstrated that they are different from an apparently identical translocation identified previously in a patient with myelodysplastic syndrome. The identification of the split YAC and small deletion should enable a more focused search for a gene or genes that may contribute to progression from chronic phase to blast crisis in CML.

Blotting, Southern↗
PubMed1991

Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis.

A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.

Adult↗
PubMed1989

Philadelphia-positive chronic myelogenous leukemia with typical bcr/abl molecular features and atypical, prolonged survival.

Despite the major breakthrough in the knowledge of the molecular events underlying the t(9;22) translocation, still no consistent data have been found on the evolution of Ph1 positive CML from the chronic to the accelerated or blastic phase of the disease. In most patients in fact the bcr/abl rearrangements are identical both in chronic phase and in blast crisis, and overall differences in chronic phase duration, related to different location of breakpoints inside the bcr region, were found to be marginal. We approached this problem by studying the molecular features of the bcr/abl abnormality in rare CML patients with very long, atypical chronic phase. The three patients studied, whose chronic phase duration is 17, 19, and 21 years, respectively, have typical genomic bcr rearrangements, and two of them show, hybridizing Northern blots to c-abl, the 8.5 kb mRNA, as that typically present in CML. It seems that genomic alterations within bcr and abl cannot account, alone, for the duration of the chronic phase of Ph1 positive CML and those quantitative and/or qualitative alterations of the p210 bcr/abl protein, unluckily awkward to prove, might be responsible for the atypical clinical features of these CML long survivors.

Adult↗
PubMed1993

Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: initial experience of the National Marrow Donor Program.

In the interval from December 1987 to November 1990, 196 consecutive patients with chronic myelogenous leukemia (CML) received unrelated donor marrow transplantation using marrow procured by the National Marrow Donor Program (NMDP) at 21 NMDP-affiliated marrow transplant centers. Baseline donor and recipient data as well as follow-up data were obtained systematically in all cases by the NMDP. The median interval from the initiation of a search for an unrelated donor to bone marrow transplantation was 8.4 months (range, 1.7 to 34.6 months). Median age of the recipients was 33.3 years (4.5 to 54.5 years). Seventy-five recipients were female and 121 were male. At time of transplant, 115 patients were in chronic phase, 51 in accelerated phase, 14 in blast crisis, and 16 in a second or subsequent chronic phase. In 133 cases, donors and recipients were identical at the HLA A, B, and DR loci using standard serologic typing, and in 63 cases, there was nonidentity at one HLA locus. Patients were prepared for transplantation with a combination of high-dose chemotherapy and total body irradiation (N = 169) or with high-dose chemotherapy only (N = 27). Thirty-five patients received marrow depleted ex vivo of T lymphocytes, whereas 161 patients received non-T-depleted marrow. One hundred seventy-four of 196 patients engrafted (absolute neutrophil count > or = 500/mm3 for 3 consecutive days). The median time to engraftment was 22 days (6 to 69 days). Twenty-two patients failed to engraft, and an additional 10 patients experienced late graft failure. The incidence of grades III or IV acute graft-versus-host disease (GVHD) was 0.54 +/- 0.10, and that of extensive chronic GVHD was 0.52 +/- 0.12. A lower incidence of both grades III and IV acute GVHD (P = .0003) and of extensive chronic GVHD (P = .01) were independently associated with use of T-depleted marrow. The actuarial incidence of hematologic relapse at 2 years is 0.11 +/- 0.06. The 2-year actuarial incidence of disease-free survival for patients transplanted in first chronic phase within 1 year of diagnosis is 0.45 +/- 0.21, in chronic phase more than 1 year from diagnosis is 0.36 +/- 0.11, in accelerated phase is 0.27 +/- 0.12, in second or subsequent chronic phase is 0.22 +/- 0.21, and in blast crisis is 0. Fifteen of 55 patients transplanted at 40 to 50 years of age survive.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1996

Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy-induced leucopenia.

Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1 alpha and IL1 beta caused a similar increase in AML blast release of IL1RA, and addition of anti-IL1 antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony-stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1 beta and soluble TNF alpha receptors increased when the leucopenic patients developed complicating bacterial infections.

Acute-Phase Reaction↗
PubMed1989

Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia.

Molecular mechanisms responsible for the clinical progression of chronic myelocytic leukemia to its accelerated phase or to blast crisis have not been defined. We found alterations of the p53 gene (p53 is a 53-kDa nuclear protein) including deletions and rearrangements in 8 of 34 patients in blast crisis and 1 of 4 patients in the accelerated phase, but in only 1 of 38 patients in the chronic phase of chronic myelocytic leukemia. Only two other examples of p53 gene alterations were found among 203 patients with hematologic malignancies and solid tumors. Transcripts of the p53 gene were uniformly found in chronic-phase cells, but gene expression was variable in blast crisis, and transcripts were reduced or undetectable in 10 of 16 patients. Heterogeneous alterations in the structure and expression of the p53 gene appear to be relatively frequent in blast crisis and may be involved in the evolution of disease.

Blast Crisis↗
PubMed1995

[Allogeneic bone marrow transplantation in chronic myeloid leukemia. The clinical results and risk factors in 70 patients].

BACKGROUND: The 10 year experience of a single center performing allogeneic bone marrow transplantation in 70 patients with chronic myeloid leukemia (CML) is analyzed. METHODS: Seventy patients transplanted for CML between November 1982 and October 1992 were evaluated. Fifty-two patients were in the first chronic phase (FC), 10 in an accelerated phase, 4 in blast crisis and 4 in the second chronic phase. The combination of cyclosporin and methotrexate was the most commonly used prophylactic schedule for graft versus host disease (GVHD) (60 cases) and T depletion was not performed in any case. The combination of cyclophosphamide (120 mg/kg) and total body irradiation was used in 48 patients with the remaining patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The estimation of survival was performed using the Kaplan-Meier limit product method. The prognostic factors influencing survival, disease free period and relapse were evaluated by Cox multivariate models of proportional risk. RESULTS: Actuarial survival at four years was 40% (95% Cl: 26-58%). Multivariate analysis selected variables associated with lower survival, the presence of acute GVHD (relative risk-RR-4.75), advanced disease phase (RR: 3.26) and age over 30 years (RR: 3.57). Eleven patients had relapsed. Multivariate analysis found the absence of chronic GVHD (RR: 5.3) and advanced phase (RR: 1.91) to be associated to a higher probability of relapse. In a separate analysis of the 48 patients transplanted in chronic phase who received cyclosporin and methotrexate, the disease free survival was longer for those under the age of 30 years (71.4% vs. 36%) without acute GVHD (68.8% vs. 39.6%) and those transplanted from a male donor (64.6% vs. 30%). CONCLUSIONS: Advanced phase of the disease, the presence of acute graft versus host disease and the age and female sex of the donor are the main factors associated to shorter survival in allogeneic bone marrow transplant for chronic myeloid leukemia. In contrast, the presence of chronic graft versus host disease decreases the possibilities of relapse.

Adolescent↗
PubMed2003

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.

BACKGROUND: Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. METHODS: We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. RESULTS: After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy. CONCLUSIONS: In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.

Adolescent↗
PubMed1988

Prediction of impending blast cell transformation in chronic granulocytic leukaemia.

Bone marrow trephine biopsy specimens from 24 patients with chronic granulocytic leukaemia were studied to identify bone marrow changes that suggest incipient or impending blast transformation. In the chronic phase of chronic granulocytic leukaemia, blasts and promyelocytes were seen predominantly in the paratrabecular and perivascular regions, while myelocytes, metamyelocytes and segmented polymorphs were seen predominantly in the central intertrabecular marrow space. The patients were divided into two equal groups according to the degree of perivascular and paratrabecular infiltration: those with minimal (one to three layers of blasts and promyelocytes) and those with marked (four to eight layers of blasts and promyelocytes) infiltration. Ten of the 12 patients in the former group did not develop blast transformation and remained in the chronic phase during a 32- to 84-week follow-up period, whereas nine of the 12 patients in the latter group developed blast transformation, with six undergoing transformation within the first 26 weeks. These findings suggest that the histomorphological pattern of bone marrow changes in chronic granulocytic leukaemia may be useful in recognizing a subset of chronic granulocytic leukaemia patients undergoing blast transformation in the ensuing 6 months.

Bone Marrow↗
PubMed2002

A novel predictive model of outcome in de novo AML based on S-phase activity and proliferative response of blast cells to haemopoietic growth factors.

This study assesses whether the kinetic response of AML cells to HGFs might help to predict initial clinical outcome of treatment in de novo AML in association with age, FAB type and karyotype. Best subset regression analysis indicated optimal variables to develop models to predict prognosis. High S-phase in surviving cells following 7 days incubation in SFM, resistance to stimulation by G+GM-CSF and poor karyotype taken in combination correctly predicted outcome in 83% of patients. The importance of high SFM S-phase may be to indicate autonomous proliferation therefore a leukemic clone more likely to regenerate following therapy at the expense of normal haemopoiesis. Kinetic studies of AML cells may be a useful predictor of outcome in addition to other more established prognostic factors.

Adult↗
PubMed1982

Sequential vincristine, arabinosylcytosine and adriamycin in acute leukemia: cytologic and cytokinetic studies.

Cytokinetic and cytocidal effects exerted on peripheral blood blasts by sequential administration of vincristine (VCR) 2 mg on day 1, arabinosylcytosine (Ara-c) 50-60 mg/m2/12 hr from day 2-4), and Adriamycin (ADM, Farmitalia, Milan, Italy, 40-60 mg/m2 on day 5) have been examined in 22 courses of treatment performed on 12 patients with nonlymphoblastic and in 4 with lymphoblastic acute leukemia. In 4 patients, the bone marrow blasts wee examined before and also after VCR-Ara-c administration. In vitro tritiated thymidine autoradiography and propidium iodide-DNA flow cytometry were employed for kinetic studies. Blasts disappeared from blood with a median half time of 35 hr. After VCR-Ara-c administration, a significant increase in labeling index (LI) and in the aliquot of cells with DNA content between the diploid (2n) and the tetraploid (4n) values was observed in 80% of the courses in peripheral blood blasts and in all courses in bone marrow blasts. The median grain count over the labeled nuclei was decreased, and the 4n cell percentage and the bone marrow blast mitotic index did not increase. These findings suggest that the increase in the S phase fraction of blast population is due to cell synchronization. Increase in the S phase appears to heighten the cytocidal effect of ADM. The aliquot of the blasts cleared from blood after ADM were in fact related directly to the degree of labeling index increase observed during the previous administration of VCR and Ara-c.

Acute Disease↗
PubMed1981

Cytogenetic observations in chronic myeloid leukemia (CML) correlations of the cytogenetic findings with morphological cytochemical features of blast cells in various types of blastic phase.

Forty-nine cases of chronic myeloid leukemia have been investigated using cytogenic methods. Twenty-six patients were studied in chronic phase, twenty-three during the transformation of the disease. Out of the second group of the patients, nine were myeloid, five myelomonocytic, two promyelocytic, two megakaryoblastic and five lymphoid in their morphological and cytochemical appearance. Some correlation could be observed between the clinical, morphological, cytological and cytogenetic findings of different subgroups of the blastic phase in CML. The results demonstrate the divergent clonal evolution of transformed blast cells, and emphasize the importance of chromosome investigations -- in addition to the early diagnosis of metamorphosis -- in distinguishing the different subgroups of the terminal stage of CML.

Adult↗
PubMed2006

Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.

BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)

Antineoplastic Agents↗
PubMed1987

Treatment of chronic myelogenous leukemia with recombinant interferon alfa-2b.

Interferon alfa-2b (Intron A; Schering-Plough) was administered to 36 patients with chronic myeloid leukemia (CML) at an initial dose of 4 X 10(6) IU/m2 daily subcutaneously, adapted to changes in leukocyte counts during the course of treatment. Of 32 patients who could be fully evaluated (20 men and 12 women; median age, 34 years) 29 were in the chronic phase, one had a blast crisis and two had accelerated phase disease. Hematologic remission was achieved in 20 of the 32 patients, while a partial hematologic remission was obtained in 10. Elevated pretreatment white-cell counts returned to normal in 25 patients after 3-40 weeks. There was a parallel decrease in platelet counts after an average treatment time of six weeks and in lactate dehydrogenase, after 2-20 weeks. In conclusion, administration of interferon alfa-2b resulted in a relatively rapid cell reduction in chronic phase CML. The long-term effect of this treatment on the course of the disease and the place of interferon alfa-2b in the overall concept of CML treatment remains to be evaluated.

Adult↗
PubMed1967

Studies of cellular proliferation in human leukemia. I. Estimation of growth rates of leukemic and normal hematopoietic cells in two adults with acute leukemia given single injections of tritiated thymidine.

Two adults with rapidly progressive acute myeloblastic and myelomonoblastic leukemia were given single injections of tritiated thymidine, and measurements were made of the growth rates of their leukemic and normal hematopoietic cells by radioautographic methods. Although almost all leukemic blasts in both marrow and blood were metabolically active as shown by their ability to incorporate tritiated uridine and leucine in vitro, only 5.6% and 6.1% of the blasts in the marrow and even fewer in the blood incorporated tritiated thymidine. The mitotic indexes of the marrow blasts were 0.66% and 0.52%; no circulating blasts were dividing. The mean generation times of the actively proliferating blasts were estimated to be 49 and 83 hours. This cannot be equated with the doubling time of the total leukemic population as there is evidence that many blasts fail to continue dividing and die. The mean durations of the phases of the blasts' mitotic cycles were as follows: DNA synthesis (S) = 22 and 19 hours, premitosis (G(2)) = 3 hours, mitosis (M) = 0.47 and 0.62 hour (minimal estimates), and postmitosis (G(1)) = 24 and 61 hours. In both patients the maximal mean transit time of the blasts in the blood was 36 hours, and the minimal numbers of actively dividing blasts present were 1.6 and 2.6 x 10(9) per kg of body weight.Estimates were also made of the rates of proliferation and maturation of the residual normal erythrocytic and granulocytic cells in these two patients. Although total production was markedly diminished because of reduction in the number of normal elements, the relatively few remaining normal cells appeared to be dividing and maturing at rates that are about the same or only slightly slower than those found in normal subjects. We conclude that main reason leukemic blasts displace normal hematopoietic precursors in acute leukemia is that the blasts largely fail to differentiate. Many die but many others persist in the marrow and elsewhere as primitive cells and continue to proliferate. As the blasts accumulate, they gradually displace the normal hematopoietic cells, most of which continue their normal course of differentiation and leave the marrow as nondividing mature cells. It is not known why the over-all production of normal cells is not adequately increased to compensate for the anemia, granulocytopenia, and thrombocytopenia that develop, but apparently the leukemic cells somehow interfere with the proliferation or differentiation or both of normal stem cells.

Autoradiography↗
PubMed1991

Treatment with interleukin-3 plus granulocyte-macrophage colony-stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts.

Hematopoietic growth factors (HGFs) interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) individually have been shown to increase the percentage of acute myeloid leukemia (AML) blasts in S phase and enhance the cytotoxic effects of Ara-C against these blasts in culture. We compared in vitro the effects of a combined treatment with GM-CSF (10 ng/mL) plus IL-3 (10 ng/mL) on the metabolism and cytotoxicity of Ara-C in normal bone marrow mononuclear cells (NBMMC) and AML blasts. NBMMC from six healthy volunteers and AML blasts from 10 patients were incubated for 20 hours with or without IL-3 plus GM-CSF, followed by a concurrent treatment with Ara-C for 4 additional hours. Exposure to the HGFs and Ara-C produced significantly higher intracellular Ara-CTP levels as well as higher Ara-CTP/dCTP pool ratios in AML blasts as compared with NBMMC. Treatment with HGFs resulted in [3H] Ara-C DNA incorporation that was significantly higher in AML blasts versus NBMMC. This selective improvement of Ara-C metabolism in AML blasts was associated with an enhanced Ara-C-mediated leukemia colony-forming unit (CFU) growth inhibition. In contrast, exposure to HGFs resulted in an improved colony growth of normal CFU granulocyte-monocyte and CFU-granulocyte, erythroid, monocyte, megakaryocyte. These in vitro studies indicate that a combined treatment with IL-3 plus GM-CSF may improve the selectivity of Ara-C against AML blasts.

Acute Disease↗
PubMed2003

[Detecting methylation of the calcitonin gene in monitoring treatment and disease evolution for myelogenous leukemia].

BACKGROUND & OBJECTIVE: Calcitonin gene mostly appears hypomethylation in normal cells. Hypermethylation of calcitonin gene frequently implies malignancy transformation and is probably related to the progress of hematological malignancy tumors. However, studies on the significance of hypermethylation of calcitonin gene in the diagnosis and treatment of myelogenous leukemia were rarely reported. This study was designed to investigate the value of analyzing hypermethylation of the calcitonin gene for detecting minimal residual disease (MRD) and monitoring disease evolution in acute myeloid leukemia (AML) and chronic myeloid leukemia(CML). METHODS: Digestion of DNA with Hpa II in combination with polymerase chain reaction (PCR) was used to examine the methylation patterns of the calcitonin gene in 31 cases with AML, 45 cases with CML (including 33 patients in chronic phase, 2 in accelerated phase, and 10 in blast crisis), and 14 healthy adults (used as control). RESULTS: The hypermethylation of calcitonin gene was found in 25 of 31 cases with AML (80.6%), 0 of 14 healthy adults (0%) (P< 0.01). Follow-up study of 5 cases with AML showed that 4 cases who appeared hypermethylation of calcitonin gene at both diagnosis and complete remission relapsed 3, 5, 6, and 14 months respectively after complete remission; the other case without hypermethylation of calcitonin gene did not relapse 25 months after complete remission. Among 45 cases with CML, 3 of 33 in chronic phase, 2 of 2 in accelerated phase and 8 of 10 in blast crisis showed hypermethylation of calcitonin gene; there were significant differences between chronic phase group and blast crisis group (including accelerated phase) (P< 0.01); three cases with CML in chronic phase developed into blast crisis 10, 12, and 13 months after hypermethylation of calcitonin gene were detected. CONCLUSION: Analyzing hypermethylation of calcitonin gene may be useful in assessing the prognosis of AML and monitoring disease evolution in CML.

Adolescent↗
PubMed2001

Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo.

STI571 targets p210(BCR-ABL) in chronic myeloid leukaemia (CML). In vitro, STI571 reduces self-replication (replating ability) by chronic-phase CML CFU-GM. Here, we studied CFU-GM in advanced-phase (accelerated and blast crisis) CML. The numbers and self-replication of CFU-GM in advanced phase were greater than in the chronic phase. Self-replication by CFU-GM from advanced phase patients was reduced by STI571 or IFN alfa to the same extent as in the chronic phase. The reduced replating ability induced by STI571 correlated with that induced by IFN alpha (r=0.73). STI571 treatment in vivo also reduced replating ability and the numbers of CFU-GM/ml of blood.

Antineoplastic Agents↗