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Blast crisis (BC) is one of the most dreaded complications of chronic myeloid leukemia (CML). Fortunately, the incidence of BC has diminished markedly in the BCR-ABL tyrosine kinase inhibitor (TKI) era. The primary objective of initial treatment in BC is to achieve a second chronic phase (CP) and to proceed to an allogeneic stem cell transplantation (SCT) in eligible patients. The clinical outcome of patients with CML BC remains unsatisfactory, even with highly potent TKIs, as remissions are short lived and there is an unmet need for novel therapies. We provide a comprehensive summary reviewing the current management of Lymphoid BC. [ABSTRACT FROM AUTHOR]

Background: The vast majority of chronic myeloid leukemia (CML) patients have a single translocation t(9;22)(q34;q11), BCR/ABL1 fusion genes, which is regarded as the hallmark of CML. However, around 5 to 10% of CML patients exhibit the involvement of a third chromosome. In some very rare cases a fourth or even fifth chromosome can be involved with the t(9;22). Methods: This case report is based on a 40‐year‐old Saudi Arabian male patient, diagnosed with CML in lymphoid blast crisis, and observed to have a four‐way 46 XY, t(9;22;5;2)(q34;q11.2;p13;q44) translocation. The BCR/ABL1 fusion was identified by fluorescent in situ hybridization (FISH). Additionally, the BCR/ABL1 p210 mRNA fusion transcripts were identified by a molecular test. Results: The clinical and prognostic impact of additional partner chromosomes to t(9;22) remains unknown. The CML patient with this novel four‐way translocation t(9;22;5;2) progressed to blast crisis and was resistant to Tyrosine Kinase Inhibitor (TKI) therapy. Therefore, this case is more in alignment with the negative impact of additional partner chromosomes to the translocation at t(9;22). Conclusion: Here we report for the first time a novel four‐way translocation at t(9;22;5;2)(q34;q11.2;p13;q44). [ABSTRACT FROM AUTHOR]

Abstract Background The vast majority of chronic myeloid leukemia (CML) patients have a single translocation t(9;22)(q34;q11), BCR/ABL1 fusion genes, which is regarded as the hallmark of CML. However, around 5 to 10% of CML patients exhibit the involvement of a third chromosome. In some very rare cases a fourth or even fifth chromosome can be involved with the t(9;22). Methods This case report is based on a 40‐year‐old Saudi Arabian male patient, diagnosed with CML in lymphoid blast crisis, and observed to have a four‐way 46 XY, t(9;22;5;2)(q34;q11.2;p13;q44) translocation. The BCR/ABL1 fusion was identified by fluorescent in situ hybridization (FISH). Additionally, the BCR/ABL1 p210 mRNA fusion transcripts were identified by a molecular test. Results The clinical and prognostic impact of additional partner chromosomes to t(9;22) remains unknown. The CML patient with this novel four‐way translocation t(9;22;5;2) progressed to blast crisis and was resistant to Tyrosine Kinase Inhibitor (TKI) therapy. Therefore, this case is more in alignment with the negative impact of additional partner chromosomes to the translocation at t(9;22). Conclusion Here we report for the first time a novel four‐way translocation at t(9;22;5;2)(q34;q11.2;p13;q44).

Blast crisis (BC) is one of the most dreaded complications of chronic myeloid leukemia (CML). Fortunately, the incidence of BC has diminished markedly in the BCR-ABL tyrosine kinase inhibitor (TKI) era. The primary objective of initial treatment in BC is to achieve a second chronic phase (CP) and to proceed to an allogeneic stem cell transplantation (SCT) in eligible patients. The clinical outcome of patients with CML BC remains unsatisfactory, even with highly potent TKIs, as remissions are short lived and there is an unmet need for novel therapies. We provide a comprehensive summary reviewing the current management of Lymphoid BC.

Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML. This case illustrates the major interest of interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1 positive ALL. [ABSTRACT FROM AUTHOR]

Early recognition of children with chronic phase chronic myeloid leukaemia ( CML- CP) at risk for developing a lymphoid blast crisis (Ly BC) is desirable, because therapy options in CML- Ly BC are limited. We used Multiplex Ligation-dependent Probe Amplification to determine whether B-cell lymphoid leukaemia-specific copy number alterations ( CNAs) (e.g. IKZF1, PAX5, CDKN2A deletions) could be detected in CML- CP and may be used to predict disease progression to Ly BC. CNAs were detected in all patients with CML-Ly BC, but in none of the 77 patients with CML- CP. Based on this study we conclude that CNAs remain a hallmark of disease progression. [ABSTRACT FROM AUTHOR]

Chronic myelogenous leukemia (CML) is a common myeloproliferative disease that is characterized by the clonal expansion of marrow stem cells, and is associated with the Philadelphia chromosome. As the disease progresses, additional chromosome abnormalities may arise. The prognostic impact of secondary chromosomal abnormalities in CML is complex, heterogeneous, and sometimes related to previous treatment. Here, we describe a CML patient in lymphoid blast crisis associated with a new chromosomal abnormality identified, dic(7;12)(p12.21;p12.2) and i(12)(q10) using classical cytogenetics and spectral karyotype analysis. To the best of our knowledge, this is the first report of t(7;12)(p11.1;q11.1) and i(12)(q10) in a CML patient with lymphoid evolution. [ABSTRACT FROM AUTHOR]

There are no studies regarding analysis of clinical and haematological features of chronic myelogenous leukemia (CML) from Pakistan. This study analyzes the data of patients suffering from CML, reporting to a major referral Institute in Northern Pakistan in the past 6 years and 3 months. CML constitutes approximately 80% of all myeloproliferative disorders, with a peak incidence between 21-50 years of age, and a male:female ratio of 2:1. Anaemia and massive splenomegaly were the main clinical features found in 92% and 47% patients respectively. There was significant correlation between anaemia and WBC counts with degree of splenomegaly. Three percent of all CML patients presented as de novo accelerated phase, and another 3% presented as blast crises without any previous history of chronic phase. The ratio of myeloid and lymphoid blast crisis was 2:1. Median duration of chronic phase in patients on hydroxyurea treatment was 6 years. Thirty six percent of patients in chronic phase of CML belonged to intermediate and high risk according to Sokal and Hasford scoring systems. In contrast to the Caucasian populations where the peak incidence of the disease is in 6th to 7th decade, CML occurs in Pakistan in a much younger population, with a broad peak between 21--50 years of age. Patients present in fairly advanced disease because of poor access to health care facilities, due to non-affordability and lack of health insurance coverage. [ABSTRACT FROM AUTHOR]

Philadelphia positive malignant disorders are a clinically divergent group of leukemias. These include chronic myeloid leukemia (CML) and de novo acute Philadelphia positive (Ph(+)) leukemia of both myeloid, and lymphoid origin. Recent whole genome screening of Ph(+)ALL in both children and adults identified an almost obligatory cryptic loss of Ikaros, required for the normal B cell maturation. Although similar losses were found in lymphoid blast crisis the genetic background of the transformation in CML is still poorly defined. We used Significance Analysis of Microarrays (SAM) to analyze comparative genomic hybridization (aCGH) data from 30 CML (10 each of chronic phase, myeloid and lymphoid blast stage), 10 Ph(+)ALL adult patients and 10 disease free controls and were able to: (a) discriminate between the genomes of lymphoid and myeloid blast cells and (b) identify differences in the genome profile of de novo Ph(+)ALL and lymphoid blast transformation of CML (BC/L). Furthermore we were able to distinguish a sub group of Ph(+)ALL characterized by gains in chromosome 9 and recurrent losses at several other genome sites offering genetic evidence for the clinical heterogeneity. The significance of these results is that they not only offer clues regarding the pathogenesis of Ph(+) disorders and highlight the potential clinical implications of a set of probes but also demonstrates what SAM can offer for the analysis of genome data. [ABSTRACT FROM AUTHOR]

Therapy with vincristine (2 mg i.v. weekly) and prednisolone (100 mg p.o. daily) caused a decrease in fibrinogen levels in nine patients treated for lymphoid blast crisis (LBC) of chronic myeloid leukemia (CML). During the first days of treatment disseminated intravascular coagulation (DIC), evidenced by a positive ethanol gelation test, markedly increased thrombin-antithrombin III complex and fibrin-split product D-dimer levels, and a rapid fall in fibrinogen levels was observed in two patients. The induction of DIC in these two patients caused profuse bleeding in one and necessitated substitution therapy with fibrinogen and platelet concentrates. The remaining seven patients revealed no signs of DIC; nevertheless, four of them showed a moderate increase in D-dimer levels after initiation of therapy. In these patients a well-known side effect of long-term steroid therapy, namely a decrease of fibrinogen levels, was observed within the first week of treatment. Fibrinogen levels did not fall below 150 mg/dl and increased after dose reduction from 100 mg/day to 50 mg/day. We conclude from our results that two types of disturbances in fibrinogen metabolism can be observed during vincristine/prednisolone therapy of LBC of CML: (a) a decrease of fibrinogen levels due to a steroid-mediated impairement of liver synthesis, and (b) a rapid fall in fibrinogen levels in the course of DIC, most likely induced by the release of procoagulants from detoriorating blast cells, leading to severe bleeding in selected cases. [ABSTRACT FROM AUTHOR]

A 34-year-old man with chronic myeloid leukaemia (CML) firstly developed a lymphoid blast crisis of B-cell type. After a second chronic phase which lasted for > 4 years with maintenance chemotherapy of hydroxyurea, 6-mercaptopurine and methotrexate, he developed a T-cell acute lymphoblastic leukaemia of TcR-γδ+ type. Cytogenetic analysis revealed disappearance of the t(9;22) translocation and appearance of new abnormalities consistent with the diagnosis secondary acute leukaemia. To our knowledge, secondary leukaemia in CML has not previously been reported. [ABSTRACT FROM AUTHOR]

The article presents information on treatment of resistant Ph+ lymphoid blast crisis of chronic myeloid leukemia. It informs about a therapy for the Ph+ lymphoid blast crisis of chronic myeloid leukemia which includes using the cancer drug dasatinib combined with vincristine. It informs about the drug as it leads to disease transformation following hematological and cytogenic remission.

An 11-year-old male was diagnosed with chronic-phase chronic myeloid leukemia (CML) in 1998 and received therapy with interferon-α2b and low-dose cytarabine. In 6 years, he progressed to lymphoid blast crisis and received induction chemotherapy with prednisolone, vincristine, daunorubicin, and l-asparaginase concomitantly with imatinib 400 mg/day, and continuation with vincristine + prednisolone, cytarabine + etoposide, vincristine + l-asparaginase, cyclophosphamide + etoposide, and 6-mercaptopurine + methotrexate. Complete molecular response (MR) was achieved and therapy was continued with imatinib 800 mg/day. He relapsed to chronic-phase CML after interruption of imatinib and regained MR after its restart. The patient is alive 17.5 years after CML diagnosis and 11.5 years after lymphoid blast crisis., (© 2016 Wiley Periodicals, Inc.)

Blast crisis (BC) is the major remaining challenge in the management of chronic myeloid leukemia (CML). The prognosis of the BC patient who carries ABL kinase mutation is very poor. One patient, with lymphoid CML-BC third time, was detected with T315A/F359I/M244V compound mutation by direct sequencing after treatment with tyrosine kinase inhibitions three years. The patient was treated with decitabine, dexamethasone, in combination with nilotinib and dasatinib. Then this patient received a complete hematologic response and cytogenetic response after two cycles of treatment., Competing Interests: Conflicts of Interest: None declared.

Early recognition of children with chronic phase chronic myeloid leukaemia (CML-CP) at risk for developing a lymphoid blast crisis (LyBC) is desirable, because therapy options in CML-LyBC are limited. We used Multiplex Ligation-dependent Probe Amplification to determine whether B-cell lymphoid leukaemia-specific copy number alterations (CNAs) (e.g. IKZF1, PAX5, CDKN2A deletions) could be detected in CML-CP and may be used to predict disease progression to LyBC. CNAs were detected in all patients with CML-LyBC, but in none of the 77 patients with CML-CP. Based on this study we conclude that CNAs remain a hallmark of disease progression., (© 2014 John Wiley & Sons Ltd.)