scholarly journals Association of a chromosomal 3;21 translocation with the blast phase of chronic myelogenous leukemia

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1338-1342 ◽  
Author(s):  
CM Rubin ◽  
RA Larson ◽  
MA Bitter ◽  
JJ Carrino ◽  
MM Le Beau ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Reciprocal Translocation ◽  
Clonal Evolution ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Cytogenetic Abnormality ◽  
Blast Phase ◽  
Male Patients

Abstract An identical reciprocal translocation between the long arms of chromosomes 3 and 21 with breakpoints in bands 3q26 and 21q22, t(3;21)(q26;q22), was found in three male patients with the blast phase of chronic myelogenous leukemia (CML). The abnormality was clonal in all three patients and was always accompanied by either a standard or variant 9;22 translocation resulting in a Philadelphia chromosome (Ph1). In two cases, the t(3;21) was the only abnormality other than a t(9;22) in the primary clone. Serial studies of one patient demonstrated that the t(3;21) occurred as a result of clonal evolution near the time of development of the blast phase. We have not observed the t(3;21) in greater than 500 patients with CML in the chronic phase. Thus, the t(3;21) is a new recurring cytogenetic abnormality associated with the blast phase of CML.

scholarly journals Association of a chromosomal 3;21 translocation with the blast phase of chronic myelogenous leukemia

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1338-1342
Author(s):  
CM Rubin ◽  
RA Larson ◽  
MA Bitter ◽  
JJ Carrino ◽  
MM Le Beau ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Reciprocal Translocation ◽  
Clonal Evolution ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Cytogenetic Abnormality ◽  
Blast Phase ◽  
Male Patients

An identical reciprocal translocation between the long arms of chromosomes 3 and 21 with breakpoints in bands 3q26 and 21q22, t(3;21)(q26;q22), was found in three male patients with the blast phase of chronic myelogenous leukemia (CML). The abnormality was clonal in all three patients and was always accompanied by either a standard or variant 9;22 translocation resulting in a Philadelphia chromosome (Ph1). In two cases, the t(3;21) was the only abnormality other than a t(9;22) in the primary clone. Serial studies of one patient demonstrated that the t(3;21) occurred as a result of clonal evolution near the time of development of the blast phase. We have not observed the t(3;21) in greater than 500 patients with CML in the chronic phase. Thus, the t(3;21) is a new recurring cytogenetic abnormality associated with the blast phase of CML.

Treatment of advanced stages of Philadelphia chromosome-positive chronic myelogenous leukemia with interferon-alpha and low-dose cytarabine.

1992 ◽  
Vol 10 (5) ◽  
pp. 772-778 ◽  
Author(s):  
H M Kantarjian ◽  
M J Keating ◽  
E H Estey ◽  
S O'Brien ◽  
S Pierce ◽  
...  
Keyword(s):  
Survival Rate ◽  
Chronic Myelogenous Leukemia ◽  
Interferon Alpha ◽  
Low Dose ◽  
Clonal Evolution ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Dose Schedule ◽  
Myelogenous Leukemia ◽  
Low Dose Cytarabine

PURPOSE To evaluate the efficacy of interferon-alpha (IFN-A) and low-dose cytarabine (ara-C) combination chemotherapy in patients with chronic myelogenous leukemia (CML). PATIENTS AND METHODS Sixty patients with advanced phases of Philadelphia chromosome (Ph)-positive CML received combination therapy with IFN-A 5 x 10(6) U/m2 daily, and low-dose ara-C 15 mg/m2 daily for 2 weeks every 4 weeks until remission, then for 1 week every month as maintenance. Forty patients were in late chronic-phase CML, and 20 were in accelerated-phase CML (16 with clonal evolution only, four with other criteria). Their outcome was compared with 58 patients (39 late chronic-phase CML and 19 accelerated-phase CML) who had been previously treated with IFN-A alone in the same dose schedule. RESULTS In late chronic-phase CML, patients receiving IFN-A plus ara-C had a better complete hematologic response (CHR) rate compared with those treated with IFN-A alone (55% v 28%; P = .02), a trend for better Ph suppression (15% v 5%; P = .13), and a longer survival (3-year survival rate 75% v 48%; P less than .01). These differences do not seem to be caused by imbalances in prognostic factors between the two treatment groups. In accelerated-phase CML, the addition of ara-C to IFN-A did not improve the response rate of treated patients, and the difference in survival was accounted for by different patient characteristics. Suppression of clonal evolution was observed in five patients (25%). Patients with clonal evolution as the only criterion for disease acceleration had a longer survival than those with other or additional accelerated-phase criteria (3-year survival rate 67% v 22%; P less than .01). CONCLUSION The results with the combination of IFN-A plus ara-C in late chronic-phase CML are encouraging, and suggest the need for its evaluation in early chronic-phase CML.

Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3547-3553 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge Cortes ◽  
Susan O'Brien ◽  
Francis J. Giles ◽  
Maher Albitar ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Response Rate ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Blast Phase ◽  
Molecular Abnormalities ◽  
Philadelphia Chromosome Positive

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

scholarly journals RAS mutations are rare events in Philadelphia chromosome-negative/bcr gene rearrangement-negative chronic myelogenous leukemia, but are prevalent in chronic myelomonocytic leukemia

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1214-1219 ◽  
Author(s):  
C Hirsch-Ginsberg ◽  
AC LeMaistre ◽  
H Kantarjian ◽  
M Talpaz ◽  
A Cork ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Point Mutations ◽  
Chronic Phase ◽  
Chronic Myelomonocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Ras Oncogene ◽  
Ras Mutations ◽  
Ras Oncogenes ◽  
Myelomonocytic Leukemia

Abstract Previous reports have indicated that mutations of the RAS oncogenes are not associated with the chronic phase of Philadelphia chromosome- positive chronic myelogenous leukemia (Ph1+ CML). However, further studies were needed to determine their association with Ph1- CML and chronic myelomonocytic leukemia (CMML). Therefore, 6 patients with Ph1- CML who were also negative for BCR rearrangements (Ph1-/BCR- CML) and 30 patients with CMML were analyzed for the presence of RAS oncogene point mutations to determine the similarities of these diseases at the molecular level. The assay used the polymerase chain reaction for amplification of the target RAS sequences and panels of specific synthetic oligonucleotide probes for hybridization to wild type and/or mutated sequences. None of the six Ph1-/BCR- CML patients had mutations in the RAS oncogenes, while 17 of 30 (57%) of the CMML patients had RAS oncogene mutations. Eighty percent of the mutations involved substitution of aspartic acid for glycine (G----A) in the 12th or 13th codons of N-ras or K-ras. Furthermore, although not statistically significant, survival studies raise the possibility of shortened survival in patients with RAS oncogene point mutations, with the average survival being 33 months for Ph1-/BCR- CML, 35 months for CMML without point mutations, and 11 months for CMML with RAS mutations. Thus, RAS mutations appear to be associated with CMML and not Ph1-/BCR- chronic phase CML, there is a high propensity for the K-ras or N-ras mutations to involve an G----A substitution in the 12th or 13th codons, and RAS mutations in CMML may relate to prognosis and require further studies.

Early treatment decisions with interferon-alfa therapy in early chronic-phase chronic myelogenous leukemia.

1998 ◽  
Vol 16 (3) ◽  
pp. 882-889 ◽  
Author(s):  
S Sacchi ◽  
H M Kantarjian ◽  
T L Smith ◽  
S O'Brien ◽  
S Pierce ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Univariate Analysis ◽  
Group Analysis ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Interferon Alfa ◽  
Myelogenous Leukemia ◽  
Costal Margin ◽  
Hematologic Response

PURPOSE To determine, in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) on interferon alfa (IFNalpha), whether combining pretreatment characteristics and early response profiles would distinguish patients with differential benefits that would allow better decisions on subsequent therapy. PATIENTS AND METHODS A total of 274 patients treated from 1982 through 1990 with IFNalpha regimens were analyzed. A second group of 137 patients treated with IFNalpha and low-dose cytarabine (ara-C) between 1990 and 1994 was later used to confirm the guidelines derived from the original study group analysis. Patients' pretreatment factors and response to IFNalpha therapy at 3, 6, and 12 months were analyzed in relation to subsequent achievement of major cytogenetic response. After univariate analysis of prognostic factors, a multivariate analysis selected, at 6 months, independent pretreatment factors that added to the response status in predicting subsequent outcome. The results were then applied at the 3- and 12-month periods and confirmed in the subsequent population. RESULTS Response to IFNalpha therapy at 3, 6, and 12 months was a significant predictor of later major cytogenetic response. The presence of splenomegaly > or = 5 cm below the costal margin (BCM) or thrombocytosis > or = 700 x 10(9)/L pretreatment added significant independent prediction to response. At 6 months, patients with a partial hematologic response (PHR) or resistant disease had a less than 10% chance of achieving a later major cytogenetic response, as were those in complete hematologic response (CHR) and who had pretreatment splenomegaly and thrombocytosis. Applying the model at 3 months showed that only patients with < or = PHR and pretreatment splenomegaly or thrombocytosis at 3 months had such a low major cytogenetic response rate. Finally, at 12 months, patients with CHR still had a 15% to 25% chance of having a major cytogenetic response later if they did not have pretreatment splenomegaly and thrombocytosis. CONCLUSION This analysis allows better selection of patients with Ph-positive CML on IFNalpha therapy for continuation of IFNalpha versus changing therapy early in the course of CML. For treatment programs that choose to change patients to other investigational therapies (eg, intensive chemotherapy and/or autologous stem-cell transplantation [SCT]), baseline outcome expectations are provided for patients continued on IFNalpha therapy, against which the results of new approaches can be compared.

scholarly journals Unusual T-Lymphoblastic Blast Phase of Chronic Myelogenous Leukemia

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Jie Xu ◽  
Shaoying Li
Keyword(s):  
Lymph Node ◽  
Chronic Myelogenous Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Imatinib Treatment ◽  
Cell Transplant ◽  
Blast Phase ◽  
History Of

T-lymphoblastic leukemia/lymphoma (T-ALL) presenting as blast phase of chronic myelogenous leukemia (CML-BP) is rare. In patients without history of CML, it is difficult to differentiate between CML-BP or de novo T-ALL. Here we reported 2 unusual cases of T-ALL presenting as CML-BP. Case 1 was a 24-year-old female with leukocytosis. Besides T-lymphoblasts (32%), her marrow exhibited some morphologic features of CML. Multiple remission or relapsing marrow had never demonstrated morphologic features of CML. Despite of imatinib treatment and stem cell transplant, she died 2.5 years later. Case 2, a 66-year-old male with diffuse lymphadenopathy, showed T-ALL in a lymph node and concurrent CML chronic phase (CML-CP) in his marrow. Same BCR-ABL1 fusion transcript with minor breakpoint was present in both the lymph node and marrow specimens. Although both cases did not have a history of CML, both cases represented T-lymphoblastic CML-BP with unusual features: Case 1 is unusual in that it presented as T-ALL with some CML morphologic feature but never showed CML-CP in her subsequent marrows biopsies; Case 2 is the first reported case of T-lymphoblastic CML-BP harboring BCR-ABL1 transcript with a minor breakpoint.

Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome–positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge E. Cortes ◽  
Susan O'Brien ◽  
Francis Giles ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Interferon Α ◽  
Combination Regimens ◽  
Philadelphia Chromosome Positive

Abstract Fifty patients with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) in early chronic phase received imatinib mesylate, 400 mg orally daily. After a median follow-up of 9 months, 49 patients (98%) achieved a complete hematologic response and 45 patients (90%) achieved a major cytogenetic response, complete in 36 patients (72%). Compared with similar patients who received interferon-α with or without hydroxyurea or other interferon-α combination regimens, those receiving imatinib mesylate had higher incidences of complete and major (Ph &lt; 35%) cytogenetic responses at 3 months (34% and 74% versus 1%-4% and 9%-24%, respectively), 6 months (52% and 80% versus 3%-7% and 11%-28%, respectively), and 9 months (60% and 77% versus 5%-11% and 14%-30%, respectively; P &lt; .001). Competitive quantitative polymerase chain reaction (QPCR) studies at 9 months showed a median QPCR value (ratio of BCR-ABL/ABL transcripts × 100) of 0.59% overall and of 0.24% (range, 0.001%-29.5%) for complete cytogenetic response.

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