scholarly journals Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Rohit Gulati ◽  
Yaser Alkhatib ◽  
Vijayalakshmi Donthireddy ◽  
Michelle Madden Felicella ◽  
Madhu P. Menon ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Clinical History ◽  
Myelogenous Leukemia ◽  
Intrathecal Methotrexate ◽  
Trisomy 8 ◽  
Blast Phase ◽  
Diagnostic Significance ◽  
Allogenic Stem Cell Transplantation

Blast phase in chronic myelogenous leukemia (CML) has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia), and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117). Fluorescence in situ hybridization (FISH) of vitreous fluid detectedBCR-ABL1gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation.

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 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 A neutrophil membrane marker reveals two groups of chronic myelogenous leukemia and its absence may be a marker of disease progression

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 343-346
Author(s):  
JI Gallin ◽  
RJ Jacobson ◽  
BE Seligmann ◽  
JA Metcalf ◽  
JH McKay ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Normal Subjects ◽  
Initial Study ◽  
Myelogenous Leukemia ◽  
Superoxide Generation ◽  
Igg1 Monoclonal Antibody ◽  
Patient Groups

An IgG1 monoclonal antibody, 31D8, that recognizes normal neutrophil (PMN) membranes, was used to study PMN from patients with chronic myelogenous leukemia (CML). Nineteen patients with Philadelphia chromosome positive CML were followed over a ten-month period and compared with 23 normals, six patients with leukemoid reactions, and eight patients with phagocytic cell defects. The percentage of PMN binding of 31D8 among normal subjects was variable about a normal distribution with an average of 95 +/- 2% of cells binding 31D8. In contrast, there were two groups of CML patients: in 14 patients 88 +/- 3% PMN bound 31D8 while in the remaining five patients only 6 +/- 6% PMN bound 31D8. PMN 31D8 binding was normal in the control patient groups. Control antibodies 7C3 (binds to PMN precursors) and OKM1 (binds to the CR3 (iC3b) receptor) bound normally to CML neutrophils. Functionally, CML cells had normal chemotaxis to several stimuli and normal superoxide generation to phorbol myristate acetate. However, superoxide production in response to fmet-leu-phe was significantly less in 31D8 negative CML PMN than both 31D8 positive CML PMN and normal PMN which contained 85% 31D8 positive and 15% 31D8 negative PMN. Clinically, 2 of 14 CML patients with 31D8 positive PMN were in blast crisis (one extramedullary) at the time of study and the other 12 patients remained clinically stable in the chronic phase during the ten months of study. In contrast, one of five patients with 31D8 negative PMN was in blast crisis at the time of study and all four of the remaining patients progressed to either the accelerated phase or blast crisis. Three of these patients died of their disease eight to ten months after their initial study. Thus, failure of CML cells to bind 31D8 may be useful for predicting which patients are likely to progress to the accelerated phase or blast crisis.

scholarly journals Loss of Imprinting in Disease Progression in Chronic Myelogenous Leukemia

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3144-3147 ◽  
Author(s):  
Gurvaneet S. Randhawa ◽  
Hengmi Cui ◽  
Janet A. Barletta ◽  
Liora Z. Strichman-Almashanu ◽  
Moshe Talpaz ◽  
...  
Keyword(s):  
Disease Progression ◽  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Stable Phase ◽  
Monoallelic Expression ◽  
Parental Origin ◽  
Specific Gene ◽  
Loss Of Imprinting

Abstract The pathophysiologic role of the Philadelphia chromosome translocation in chronic myelogenous leukemia (CML) has been known for nearly 20 years. However, the most significant morbidity and mortality in CML are caused by progression to blast crisis, about which comparatively little is known at the molecular level. Genomic imprinting is a chromosomal modification leading to parental-origin–specific gene expression in somatic cells. Recently, we and others have described loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to biallelic rather than monoallelic expression in a wide variety of solid tumors. We have now examined the imprinting status of IGF2 in samples from CML patients in stable phase, accelerated phase, and blast crisis. Five of six stable-phase patients showed normal imprinting, but LOI was found in all six cases of advanced disease (three accelerated phase, three blast crisis), which was statistically highly significant (P < .01). Thus, LOI represents a novel type of genetic alteration in CML that appears to be specifically associated with disease progression.

Concurrent Megakaryocytic and Erythroid Chronic Myelogenous Leukemia Blast Crisis

2008 ◽  
Vol 132 (6) ◽  
pp. 1021-1025
Author(s):  
Danielle E. Westfall ◽  
Ling Zhang ◽  
Sophie Song ◽  
Stephen Lee
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Clinical Course ◽  
Early Recognition ◽  
Blast Crisis ◽  
Clonal Evolution ◽  
Myelogenous Leukemia ◽  
Unique Case ◽  
Blast Phase ◽  
Aberrant Expression ◽  
Aggressive Clinical Course

Abstract Chronic myelogenous leukemia with blast crisis is seen in 15% to 20% of patients with chronic myelogenous leukemia. Chronic myelogenous leukemia with either erythroid or megakaryocytic blast crisis is not uncommon in the clinical setting. The incidence ranges from 0% to 33% in accordance with literature reports. The diagnosis of erythroid or megakaryocytic blast phase is often challenging because the percentage of blasts in the blood or bone marrow required for diagnosis has not been firmly established. Also, some myeloblasts can have aberrant expression of either erythroid or megakaryocytic markers by flow cytometry during clonal evolution. Early recognition of this entity is crucial because either megakaryocytic or erythroid blast crisis predicts an aggressive clinical course. To our knowledge, the coexistence of megakaryocytic and erythroid blasts has not been reported. We report a unique case of chronic myelogenous leukemia with this rare bilineage blast crisis in the background of dysplasia and marked myelofibrosis. Related literature is also reviewed.

An Unusual Case of Philadelphia Chromosome–Positive Chronic Myelogenous Leukemia With Trisomy 19 Presenting With Megakaryoblastosis and Myelofibrosis

2013 ◽  
Vol 137 (8) ◽  
pp. 1147-1151 ◽  
Author(s):  
Nika Aljinovic ◽  
Agata M. Bogusz ◽  
Sibel Kantarci ◽  
Thomas P. Buck ◽  
Rajan Dewar
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitors ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Life Saving ◽  
Cytogenetic Studies ◽  
Night Sweats ◽  
Infectious Etiology

Initial identification of chronic myelogenous leukemia is very important since targeted therapy leads to life-saving remission. Rarely, chronic myelogenous leukemia presents with an unusual picture, making the diagnosis challenging. We describe such a case of chronic myelogenous leukemia in blast crisis in a previously healthy 61-year-old woman. The patient presented with fever, myalgias, and night sweats and was first worked up for an infectious etiology. Because of persistent anemia, a bone marrow biopsy was performed that revealed fibrosis with increased megakaryoblasts. Even though initial cytogenetic studies could not be performed because of “dry tap” aspirate, persistent efforts for cytogenetic studies were made, including a “squeeze preparation” from the core biopsy, which revealed t(9;22)(q34;q11.2) and trisomy 19. The patient was treated with tyrosine kinase inhibitors, chemotherapy, and subsequently an allogeneic stem cell transplant. She is in persistent remission. This case illustrates a complex presentation of chronic myelogenous leukemia and provides an overview of morphologic cues and the importance of performing cytogenetic studies that led to the diagnosis.

scholarly journals Identification of molecular variants of p210bcr-abl in chronic myelogenous leukemia

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 233-236
Author(s):  
R Kurzrock ◽  
WS Kloetzer ◽  
M Talpaz ◽  
M Blick ◽  
R Walters ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
K562 Cells ◽  
Protein Product ◽  
Myelogenous Leukemia ◽  
Kinase Assay ◽  
Molecular Variants ◽  
Immune Complex Kinase Assay ◽  
Hydrophilic Domain

The aberrant abl protein product of a chronic myelogenous leukemia (CML) blast crisis cell line (K562) and of five Philadelphia chromosome- positive CML patients in blast crisis were analyzed by an immune complex kinase assay using two antipeptide sera generated against the hydrophilic domain of v-abl and a region within the third exon of the breakpoint cluster region (bcr) respectively. Both the anti-abl and anti-bcr sera detected a 210 kd band in extracts derived from K562 cells and from two CML patients with myeloid blast crisis. p210 was detected by the anti-abl but not the anti-bcr sera in three CML patients with myeloid (one patient) and lymphoid (two patients) blast crisis, indicating the absence of bcr exon 3 in this protein. Southern blot analysis on DNA derived from one of the patients in the latter group was consistent with the break on chromosome 22 occurring 5′ to bcr exon 3. Our observations demonstrate that the Philadelphia translocation results in the generation of a chimeric bcr-abl protein with at least two molecular variants, both of which are enzymatically active as protein kinases.

scholarly journals Incidence of involvement of the B and T lymphocyte lineages in chronic myelogenous leukemia

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1053-1061 ◽  
Author(s):  
M Nitta ◽  
Y Kato ◽  
A Strife ◽  
M Wachter ◽  
J Fried ◽  
...  
Keyword(s):  
B Cells ◽  
Cell Lines ◽  
Chronic Myelogenous Leukemia ◽  
T Lymphocyte ◽  
B Lymphocyte ◽  
Blast Crisis ◽  
Interleukin 2 ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia

Peripheral blood specimens were obtained from 22 patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) (16 in chronic phase, 2 in an accelerated phase, and 4 in blast crisis). Studies were performed to determine the frequency of the presence of the Ph1 chromosome in cells of lymphoid lineages. Rosetted (E+) lymphocytes (T lymphocytes) from nine patients in chronic phase and one patient in blast crisis were stimulated with T cell growth factor interleukin 2 (IL-2) and/or phytohemagglutinin (PHA). All ten patients had sufficient T lymphocyte metaphases for analysis and of a total of 461 metaphases examined, only one contained the Ph1 chromosome. Nucleated cells of density less than 1.077 g/mL were infected with Epstein-Barr virus (EBV). Following infection, cell lines were established from individual colonies attached to egg albumin- coated Lab-Tek slide chambers (clonal cell lines) or from suspension culture in 96-well tissue culture cluster dishes (nonclonal cell lines). Cell surface and intracellular marker analysis confirmed the B lymphocyte phenotype of all the cell lines examined. B lymphoblastoid cell lines were established from 16 of the 22 patients. All lines from 12 patients were Ph1-negative. From two chronic phase patients, both Ph1-positive and Ph1-negative lines were established. From one patient in an accelerated phase, only Ph1-positive lines were established. From another patient in blast crisis (of myeloblastic phenotype), only Ph1- positive lines were established initially; however, five months later, after the patient had been treated with mitoxantrone, only Ph1-negative lines were derived from this patient. Based on these results, it appears that most B cells and mature T cells in most CML patients are Ph1-negative, but that about 25% of patients have predominantly Ph1- positive B cells or a mixture of Ph1-positive and Ph1-negative B cells that are capable of growing as established cell lines after transformation with EBV.

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