544 results on '"Blastic Phase"'
Search Results
2. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib
- Author
-
National Cancer Institute (NCI)
- Published
- 2020
3. Chronic myeloid leukemia coexisting with non-Hodgkin's lymphoma: An uncommon presentation of bilineage hematological malignancy.
- Author
-
Benjamin, Augustine, Adeshola, Adebayo, Fatima, Abdulrahman, John, Johnson, Akintunde, Akinrinmade, Mohammed, Ibrahim, Benedict, Amalimeh, Jatau, Abdullahi, and Haruna, Muktar
- Subjects
- *
CHRONIC myeloid leukemia , *NON-Hodgkin's lymphoma , *HEMATOLOGIC malignancies , *HYDROXYUREA , *PREDNISOLONE - Abstract
The incidence of hematological malignancies is on the rise particularly in developing countries as a result of newer diagnostic technologies and skills. However, the coexistence of chronic myeloid leukemia (CML) and non-Hodgkin lymphoma (NHL) in a single patient simultaneously is extremely rare, with an overall incidence of less than 1%, while the majority of cases (66%) have sequential presentations. We report a 36-year old Nigerian man, who was diagnosed in our facility initially in chronic phase CML, but progressed through accelerated phase to blastic phase CML and was subsequently diagnosed with NHL within weeks of starting hydroxyurea. He also received cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone (CHOP) for the NHL. However, he subsequently succumbed to the disease. CML is a triphasic disease with the tendency to acquire new cytogenetic abnormalities particularly transformation to extramedullary disease during its blastic phase. These events may be associated with NHL in the setting of blast crisis. Our case report adds to the growing literature on the coexistence of two separate hematological malignancies in a single patient. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia
- Published
- 2015
5. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase
- Published
- 2015
6. Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases
- Published
- 2014
7. Lymphoblastic predominance of blastic phase in children with chronic myeloid leukaemia treated with imatinib: A report from the I-CML-Ped Study.
- Author
-
Meyran, Deborah, Petit, Arnaud, Guilhot, Joelle, Suttorp, Meinolf, Sedlacek, Petr, De Bont, Eveline, Li, Chi Kong, Kalwak, Krzysztof, Lausen, Birgitte, Culic, Srdjana, de Moerloose, Barbara, Biondi, Andrea, and Millot, Frédéric
- Subjects
- *
IMATINIB , *TREATMENT of chronic myeloid leukemia , *CONFIDENCE intervals , *DATABASES , *HEMATOPOIETIC stem cell transplantation , *SURVIVAL , *PROTEIN-tyrosine kinase inhibitors , *TREATMENT effectiveness , *DISEASE progression , *DESCRIPTIVE statistics , *PHARMACODYNAMICS , *CHILDREN ,THERAPEUTIC use - Abstract
Chronic myeloid leukaemia (CML) is a rare disease in children. The frequency and outcome of children evolving to accelerated phase (AP) or blastic phase (BP) under treatment with imatinib is unknown. The aim of the current study is to assess the incidence of progression from CML in chronic phase with imatinib frontline in a paediatric setting and describe the management and outcome of these patients. In the I-CML-Ped Study database (www.clinicaltrials.gov , #NCT01281735), 19 of 339 paediatric patients in chronic phase treated with imatinib in the frontline evolved to CML-AP or CML-BP. With a median follow-up of 38 months (range: 2–190 months), the cumulative incidence of progression at 1 and 3 years was 3% (confidence interval [CI] 95%: 1–5%) and 7% (CI 95%: 4–11%), respectively. We observed a large predominance of lymphoid-BP (70%) over myeloid-BP (30%) with imatinib in frontline therapy. Sixteen patients underwent haematopoietic stem cell transplantation, and eight were treated with a tyrosine kinase inhibitor after transplant. Only the transplanted patients are alive. The 5-year overall survival rate of children with CML-AP/BP is 44%, with no statistical difference between the lymphoid-BP and myeloid-BP outcome. Children evolving to AP or BP under treatment with imatinib have a very poor prognosis with an overall survival under 50%, much worse than children with advanced phase at diagnosis. • Progression of chronic myeloid leukaemia in children under imatinib treatment. • Incidence of progression at 1 and 3 years is 3% and 7%, respectively. • Lymphoid phenotype predominance in blastic phase with upfront imatinib treatment. • Poor outcome when transformation occurs while on tyrosine kinase inhibitor therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
8. The Outcomes of Ponatinib Therapy in Patients With Chronic Myeloid Leukemia Resistant or Intolerant to Previous Tyrosine Kinase Inhibitors, Treated in Poland Within the Donation Program
- Author
-
Monika Joks, Renata Kasza, Janusz Kloczko, Edyta Paczkowska, R. Kroll-Balcerzak, Elżbieta Patkowska, Olga Grzybowska-Izydorczyk, Monika Biernat, Ryszard Wichary, Wioletta Makowska, Joanna Gora-Tybor, Tomasz Sacha, Malgorzata Wach, Małgorzata Kopera, Marta Oller, Aleksandra Kostyra, Hanna Ciepluch, Joanna Niesiobedzka-Krezel, Joanna Wasilewska, Anna Rudkowska-Kazanowska, Magdalena Swiniarska, Grazyna Bober, Paulina Dumnicka, Witold Prejzner, Ewa Wasilewska, Tomasz Gromek, Elżbieta Szczepanek, and Justyna Gil
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents ,Blastic Phase ,chemistry.chemical_compound ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,In patient ,Protein Kinase Inhibitors ,Accelerated phase ,Retrospective Studies ,ABL ,business.industry ,Ponatinib ,Imidazoles ,Myeloid leukemia ,Retrospective cohort study ,Hematology ,Pyridazines ,chemistry ,Drug Resistance, Neoplasm ,Poland ,business ,Tyrosine kinase - Abstract
Introduction: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML. Patients and methods: This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers. Results: For patients who started treatment with ponatinib in chronic phase (CP) (n=23) and in accelerated phase (AP) (n=3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation – none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%. Conclusion: Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups. Microabstract: Ponatinib is a new pan-inhibitor of tyrosine kinase active in resistant chronic myeloid leukemia (CML). Evaluation of outcomes in 43 patients confirmed ponatinib efficacy in a significant proportion of subjects heavily pre-treated with tyrosine kinase inhibitors achieving durable responses in both chronic phase and accelerated/blastic phase CML groups.
- Published
- 2022
9. Treatment of Philadelphia-negative myeloproliferative neoplasms in accelerated/blastic phase with azacytidine. Clinical results and identification of prognostic factors.
- Author
-
Andriani, Alessandro, Elli, Elena, Trapè, Giulio, Villivà, Nicoletta, Fianchi, Luana, Di Veroli, Ambra, Niscola, Pasquale, Centra, Antonia, Anaclerico, Barbara, Montanaro, Guido, Martini, Vincenza, Aroldi, Andrea, Carmosino, Ida, Voso, Maria Teresa, Breccia, Massimo, Montanaro, Marco, Foà, Roberto, and Latagliata, Roberto
- Subjects
MYELOFIBROSIS ,TUMORS ,CANCER treatment ,IDENTIFICATION - Abstract
There have been some reports on a possible role of azacytidine (AZA) in the treatment of accelerated/blastic phase evolved from Philadelphia-negative myeloproliferative neoplasms (MPN-AP/BP), but results are conflicting. In this study, we analyzed a cohort of 39 patients with MPN-AP/BP treated frontline with AZA at the standard dosage (75 mg/m2 ). Median time from diagnosis to AP/BP evolution was 92.3 months (IR 29.9-180.1). All patients were evaluable for hematologic response: two patients (5.2%) died early after AZA initiation, 13 patients (33.3%) had a progressive or stable disease, nine (23.1%) had a hematologic improvement (HI), seven (17.9%) achieved a partial response (PR), and eight (20.5%) a complete response (CR). Overall, 24 patients achieved a clinical hematologic response (HI + PR + CR), with an overall response rate of 61.5%. Median overall survival (OS) from AZA start of the whole cohort was 13.5 months (95% CI, 8.2-18.7). There was no difference in median OS among patients with HI, PR, or CR (P = .908). These three subgroups as "responders" having been considered, a significantly better OS was observed in responder compared with nonresponder patients, with a median OS of 17.6 months (95% CI, 10.1-25.0) versus 4.1 months (95% CI, 0.4-10.0) (P = .001) Only female gender was significant for both achievement of response (.010) and OS duration (P = .002). In conclusion, AZA is useful for the management of MPN-AP/BP, with an overall response rate (HI + PR + CR) of 61.5% and a longer OS in responders. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
10. Outcome of Ph negative myeloproliferative neoplasms transforming to accelerated or leukemic phase.
- Author
-
Mollard, Lise-Marie, Chauveau, Aurélie, Boyer-Perrard, Françoise, Douet-Guilbert, Nathalie, Houot, Roch, Quintin-Roué, Isabelle, Couturier, Marie-Anne, Dagorne, Anaig, Malou, Mohamed, Le Calloch, Ronan, Luycx, Odile, Thepot, Sylvain, Hunault, Mathilde, Guillerm, Gaelle, Berthou, Christian, Ugo, Valérie, Lippert, Éric, and Ianotto, Jean-Christophe
- Subjects
- *
MYELOPROLIFERATIVE neoplasms , *LEUKEMIA , *AZACITIDINE , *CANCER chemotherapy , *STEM cell transplantation - Abstract
Myeloproliferative neoplasms (MPN) are chronic disorders that can sometimes evolve into accelerated or leukemic phases. We retrospectively identified 122 patients with such blastic phases. The overall median survival was four months: 10.2 months for patients treated with intensive treatments compared to three months for best supportive care (p = .005). Azacytidine, intensive chemotherapies, or allogeneic stem cell transplantation gave the highest median survivals with 9, 10.2, and 19.4 months, respectively. Accelerated phases (AP) had a longer median survival compared to acute leukemia (4.8 months vs. 3.1 months; p = .02). In this retrospective and observational study, we observe that the longest survivals are seen in patients eligible for intensive treatments. Azacytidine shows interesting results in patients non-fit for intensive chemotherapy. Supportive care should probably be restricted to elderly patients and those with unfavorable karyotype. An early diagnosis of AP could also result in a better survival rate. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
11. Tyrosine Kinase Targeted Treatment of Chronic Myelogenous Leukemia and Other Myeloproliferative Neoplasms
- Author
-
Bisen, Ajit, Claxton, David F., and El-Deiry, Wafik S, editor
- Published
- 2013
- Full Text
- View/download PDF
12. Molecular Biology of Chronic Myeloid Leukemia
- Author
-
Sacha, Tomasz, Foryciarz, Kajetana, Skotnicki, Aleksander B., Witt, Michal, editor, Dawidowska, Malgorzata, editor, and Szczepanski, Tomasz, editor
- Published
- 2012
- Full Text
- View/download PDF
13. The remarkable response to ponatinib therapy in a child with blastic phase of chronic myeloid leukemia.
- Author
-
Aksu, Tekin, Ünal, Şule, and Gümrük, Fatma
- Abstract
Background. Chronic myeloid leukemia (CML) rarely occurs in children and adolescents, which shows more aggressive features like high risk of more advanced disease at the time of diagnosis. Suboptimal response to tyrosine kinase inhibitors (TKIs), adverse events, or advanced disease may impede the treatment. Case. Herein we present a nine-year-old chronic phase CML case. He had no major molecular response (MMR) to imatinib, which was switched to dasatinib. MMR was ensured for 24 months, yet he developed a lymphoid blastic phase under dasatinib. He obtained a remarkable response to ponatinib when administered in parallel to multiagent induction chemotherapy. Conclusion. Ponatinib therapy is effective and promising as a bridge to hematopoietic stem cell transplantation in children. Although more studies are necessary to determine indications, dose, efficacy, and safety data. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
14. Imaging of the Sacrum
- Author
-
Choi, Andrew Y., Ortiz, A. Orlando, Katz, Douglas S., Lypen, Steven J., Baert, A. L., editor, Knauth, M., editor, Sartor, K., editor, Van Goethem, Johan W. M., editor, van den Hauwe, Luc, editor, and Parizel, Paul M., editor
- Published
- 2007
- Full Text
- View/download PDF
15. Bosutinib as a fourth-line therapy for a patient with T315I-positive lymphoid blastic phase chronic myeloid leukemia: A case report.
- Author
-
YUKIKO KOMENO, NAOYUKI UCHIDA, YUMIKO SATOH, HIDEKI URYU, YUKO IWATA, AKIKO MASUDA, KUNIKO IIHARA, YUTAKA YATOMI, SHUICHI TANIGUCHI, and TOMIKO RYU
- Subjects
- *
PROTEIN-tyrosine kinase inhibitors , *TREATMENT of chronic myeloid leukemia , *CHRONIC myeloid leukemia , *DASATINIB , *CANCER chemotherapy , *DIAGNOSIS , *THERAPEUTICS - Abstract
A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper-cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir. Bone marrow (BM) aspiration and biopsy revealed hypercellular marrow filled with blasts. Sequencing of the leukemia cells revealed overlapping peaks for the wild-type sequence and the T315I mutant sequence. The patient was treated with 500 mg bosutinib (which was later reduced to 300 mg) for pretransplant cytoreduction. After 5 months, the patient's spleen exhibited a reduction in volume and the percentage of blasts in the BM decreased from 96.1 to 17.5%. The patient successfully underwent cord blood transplantation. The patient has been disease-free for 5 months subsequent to transplantation. This case suggests that bosutinib may be effective for cytoreduction prior to stem cell transplantation, unless the leukemia cells consistently harbor the T315I mutation. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
16. Lymphoblastic predominance of blastic phase in children with chronic myeloid leukaemia treated with imatinib: A report from the I-CML-Ped Study
- Author
-
Petr Sedlacek, Krzysztof Kałwak, Arnaud Petit, Chi Kong Li, Joelle Guilhot, Frédéric Millot, Eveline S. J. M. de Bont, Barbara De Moerloose, Meinolf Suttorp, Andrea Biondi, Deborah Meyran, Srdjana Culic, Birgitte Lausen, Université de Paris (UP), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Meyran, D, Petit, A, Guilhot, J, Suttorp, M, Sedlacek, P, De Bont, E, Li, C, Kalwak, K, Lausen, B, Culic, S, de Moerloose, B, Biondi, A, and Millot, F
- Subjects
Male ,0301 basic medicine ,Cancer Research ,[SDV]Life Sciences [q-bio] ,RECOMMENDATIONS ,Tyrosine-kinase inhibitor ,Chronic myeloid leukaemia ,Children ,Accelerated phase ,Blastic phase ,Tyrosine kinase inhibitors ,Haematopoietic stem cell transplantation ,0302 clinical medicine ,hemic and lymphatic diseases ,Cumulative incidence ,Lymphocytes ,Child ,Incidence (epidemiology) ,CHRONIC MYELOGENOUS LEUKEMIA ,3. Good health ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Female ,PROGNOSTIC DISCRIMINATION ,medicine.drug ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Accelerated phase, Blastic phase, Children, Chronic myeloid leukaemia, Haematopoietic stem cell transplantation, Tyrosine kinase inhibitors ,Blastic Phase ,DIAGNOSIS ,03 medical and health sciences ,ADHERENCE ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,MANAGEMENT ,medicine ,Humans ,neoplasms ,business.industry ,Infant ,Imatinib ,KINASE INHIBITOR ERA ,YOUNGER PATIENTS ,medicine.disease ,RANDOMIZED CML ,Transplantation ,030104 developmental biology ,Blast Crisis ,FOLLOW-UP ,business ,Chronic myelogenous leukemia ,Rare disease - Abstract
Background: Chronic myeloid leukaemia (CML) is a rare disease in children. The frequency and outcome of children evolving to accelerated phase (AP) or blastic phase (BP) under treatment with imatinib is unknown. The aim of the current study is to assess the inci-dence of progression from CML in chronic phase with imatinib frontline in a paediatric setting and describe the management and outcome of these patients.Patients and methods: In the I-CML-Ped Study database (www.clinicaltrials.gov, #NCT01281735), 19 of 339 paediatric patients in chronic phase treated with imatinib in the frontline evolved to CML-AP or CML-BP.Results: With a median follow-up of 38 months (range: 2-190 months), the cumulative inci-dence of progression at 1 and 3 years was 3% (confidence interval [CI] 95%: 1-5%) and 7% (CI 95%: 4-11%), respectively. We observed a large predominance of lymphoid-BP (70%) over myeloid-BP (30%) with imatinib in frontline therapy. Sixteen patients underwent haemato-poietic stem cell transplantation, and eight were treated with a tyrosine kinase inhibitor after transplant. Only the transplanted patients are alive. The 5-year overall survival rate of children with CML-AP/BP is 44%, with no statistical difference between the lymphoid-BP and myeloid-BP outcome.Conclusion: Children evolving to AP or BP under treatment with imatinib have a very poor prognosis with an overall survival under 50%, much worse than children with advanced phase at diagnosis. (c) 2020 Elsevier Ltd. All rights reserved.
- Published
- 2020
17. Reconstitution of NK cells expressing KIR3DL1 is associated with reduced NK cell activity and relapse of CML after allogeneic hematopoietic stem cell transplantation
- Author
-
Toshihiko Ando, Koichi Oshima, Shinya Kimura, Hiroshi Ureshino, Yuki Miyazaki, Keisuke Kidoguchi, Yasushi Kusunoki, Haruhiko Sano, Kensuke Kojima, Kana Kusaba, Hiroto Kojima, Hidenori Tanaka, Hiroh Saji, Takero Shindo, Hidekazu Itamura, and Yasushi Kubota
- Subjects
medicine.medical_specialty ,Hematology ,business.industry ,medicine.medical_treatment ,Myeloid leukemia ,Hematopoietic stem cell transplantation ,Blastic Phase ,Donor Lymphocytes ,Histocompatibility ,surgical procedures, operative ,Antigen ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Cancer research ,Medicine ,business ,KIR3DL1 - Abstract
Although the prognosis of chronic myeloid leukemia (CML) in blastic crisis remains poor, some patients achieve long-term remission after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This may be attributable to graft-versus-leukemia (GVL) effects by donor lymphocytes, but their regulating mechanisms are unclear. Antitumor natural killer (NK) cell immunity is assumed to be important in CML, and we have previously shown that allelic polymorphisms of killer immunoglobulin-like receptors (KIRs) and histocompatibility leukocyte antigens (HLAs) are associated with the response of CML to tyrosine kinase inhibitors. Here, we report a case of CML in blastic phase who received HLA-matched but KIR3DL1 allelic-mismatched allo-HSCT. After transplant, decreased BCR-ABL transcript levels and enhanced NK cell activity were transiently observed. However, reconstitution of KIR3DL1-expressing NK cells occurred, which was associated with diminished NK cell activity and increased BCR-ABL. This case indicates the potential significance of KIR3DL1 in NK cell-mediated GVL activity following allo-HSCT. To the best of our knowledge, this is the first report to analyze the association between sequential KIR3DL1 expression and activity of NK cells after allo-HSCT. Selecting donors with KIR3DL1-null alleles may maintain competent GVL effects and provide improved outcomes in allo-HSCT for CML.
- Published
- 2019
18. Advanced and Terminal Phase of B-Cell Chronic Lymphocytic Leukemia
- Author
-
Rak, K., Kiss, A., Telek, B., and Fleischer, J., editor
- Published
- 1993
- Full Text
- View/download PDF
19. Clinical Study with Human Recombinant Interferon-α2a in Chronic Myeloid Leukemia. Protocol of the Italian Cooperative Study Group on Chronic Myeloid Leukemia: Preliminary Analysis of Results
- Author
-
Tura, S. and Fleischer, J., editor
- Published
- 1993
- Full Text
- View/download PDF
20. Monoclonal Blast Cell Proliferation in Transient Myeloproliferative Disorders
- Author
-
Miyashita, T., Mizutani, S., Asada, M., Fujimoto, J., Inaba, T., Furukawa, T., Neth, Rolf, editor, Frolova, Elena, editor, Gallo, Robert C., editor, Greaves, Melvyn F., editor, Afanasiev, Boris V., editor, and Elstner, Elena, editor
- Published
- 1992
- Full Text
- View/download PDF
21. Long‐term follow‐up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic‐phase chronic myeloid leukemia
- Author
-
Kristin Anderson, Hagop M. Kantarjian, Jorge E. Cortes, Zeev Estrov, Musa Yilmaz, Alessandra Ferrajoli, Naveen Pemmaraju, Kiran Naqvi, Yesid Alvarado, Sara Dellasala, Prithviraj Bose, Philip A. Thompson, Gautam Borthakur, Jan A. Burger, Nitin Jain, Elias Jabbour, Koichi Takahashi, Jeffrey Skinner, and Shilpa Paul
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Dasatinib ,Fusion Proteins, bcr-abl ,Newly diagnosed ,Blastic Phase ,Disease-Free Survival ,Article ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Complete Cytogenetic Response ,030212 general & internal medicine ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Sulfonamides ,Dose-Response Relationship, Drug ,business.industry ,Myeloid leukemia ,Middle Aged ,Bridged Bicyclo Compounds, Heterocyclic ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Molecular Response ,Major Molecular Response ,Leukemia, Myeloid, Chronic-Phase ,Imatinib Mesylate ,Female ,business ,Follow-Up Studies ,medicine.drug - Abstract
Background Dasatinib, a potent Bcr-Abl tyrosine kinase inhibitor, is approved for the treatment of chronic-phase chronic myeloid leukemia (CML-CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100-mg daily dose. The aim of this study was to update the long-term follow-up results of dasatinib at 50 mg daily as frontline therapy for CML-CP. Methods Eighty-three patients with newly diagnosed CML-CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols. Results After a minimum follow-up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR-ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0-log reduction, and a molecular response with a 4.5-log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty-one patients (25%) had treatment interruptions for a median of 13 days (range, 4-64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow-up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2-year event-free and overall survival rates were 100%. Conclusions These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML-CP.
- Published
- 2019
22. A Case of Childhood Blastic Phase Chronic Myeloid Leukemia With Minor BCR-ABL
- Author
-
Mariko Shimizu, Hiroyuki Shichino, Hiroyuki Shimada, Maho Sato, Masami Inoue, Junko Yamanaka, and Motohiro Matsui
- Subjects
Oncology ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Fusion Proteins, bcr-abl ,Blastic Phase ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Child ,neoplasms ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Imatinib ,Hematology ,Prognosis ,Combined Modality Therapy ,Transplantation ,Dasatinib ,Haematopoiesis ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Female ,Blast Crisis ,business ,030215 immunology ,medicine.drug - Abstract
Chronic myeloid leukemia (CML) is commonly associated with major BCR-ABL transcript. We present a child with blastic phase CML associated with minor BCR-ABL transcript without prior CML diagnosis. Diagnosis was achieved by fluorescence in situ hybridization of peripheral blood neutrophils, which identified 90% as BCR-ABL positive. The patient received chemotherapy with imatinib followed by dasatinib and underwent reduced-intensity hematopoietic allogeneic stem cell transplantation with prophylactic posttransplant dasatinib for 2 years and has remained in complete molecular remission. Our intensified treatment regimen was effective compared with previous studies on minor BCR-ABL CML describing inferior outcomes with tyrosine kinase inhibitor therapy.
- Published
- 2019
23. Isolated myeloid sarcoma of the temporal bone: As the first clinical manifestation of acute myeloid leukemia in a patient of down’s syndrome
- Author
-
Namita Bhutani, Nisha Marwah, Rajeev Sen, and Archana Budhwar
- Subjects
Pathology ,medicine.medical_specialty ,Myeloid ,Down syndrome ,Granulocytic sarcoma ,Blastic Phase ,Malignancy ,Article ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Myeloid sarcoma ,Medicine ,Extramedullary ,Rhabdomyosarcoma ,Acute myeloid leukemia ,business.industry ,Myeloid leukemia ,medicine.disease ,Lymphoma ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Surgery ,business - Abstract
Highlights • MS are extremely rare tumors with an aggressive clinical course. • Morphologically, they can mimic small round cell tumors. This problem is further complicated by the lack of clinical suspicion in patients without any hematological disorder. • Accurate diagnosis of isolated MS requires a multifactorial approach including histopathology, immunophenotyping, immunohistochemistry and cytogenic abnormalities. • A high level of suspicion is necessary, because early, accurate diagnosis is important to avoid delaying appropriate chemotherapy. A delay in the diagnosis may result in unwarranted fatality particularly so in pediatric patients. • Here, we report an unusual case of MS initially presenting as a tumor of the temporal bone and first manifestation of AML, in a pediatric patient suffering from Down’s syndrome. This case illustrates the challenges associated with offering a rapid diagnosis with an early initiation of treatment., Introduction Leukemia is the most common malignancy of childhood but myeloid sarcoma is a rare presentation of underlying leukemic disorder. Myeloid sarcoma (MS) is a rare tumor composed of proliferation of myeloid precursors at extramedullary sites. Presentation of case We report an unusual case of myeloid sarcoma involving the temporal bone in a young male child who presented with a large mass involving the left temporal region. This lesion was the initial presentation which led to further diagnosis of acute myeloid leukemia in our case. This case report brings awareness to the diverse extramedullary manifestations of isolated myeloid sarcoma, as well as the importance and difficulties that are associated with establishing a rapid diagnosis and initiating treatment. Discussion They can arise de novo or in association with hematological malignancies, most commonly acute myeloid leukemia (AML-M2). Clinically, it can masquerade as an abscess, cutaneous ulcer, or as a mass lesion. Morphologically, MS can mimic a variety of small round cell tumors including lymphomas, neuroblatoma and rhabdomyosarcoma. The occurrence of this tumor usually heralds AML or the onset of the blastic phase of chronic myeloid leukemia. Early recognition of this rare entity is important, because early aggressive chemotherapy and focal irradiation can cause regression of the tumor and thus improve patient longevity. Conclusion The possibility of MS should be considered when dealing with unusual lymphoma like neoplasms that cannot be categorized as any of the Non-Hodgkin lymphoma subtypes and small blue round cell tumors.
- Published
- 2019
24. Outcome of patients with chronic myeloid leukemia in lymphoid blastic phase and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with hyper-CVAD and dasatinib
- Author
-
Koichi Takahashi, Naval Daver, Kiyomi Morita, Tapan M. Kadia, Courtney D. DiNardo, Nitin Jain, Ghayas C. Issa, Elias Jabbour, Koji Sasaki, Marina Konopleva, Farhad Ravandi, Guillermo Montalban Bravo, Guillermo Garcia-Manero, Nicholas J. Short, Hagop M. Kantarjian, and Jorge E. Cortes
- Subjects
Cancer Research ,medicine.medical_specialty ,Myeloid ,Cyclophosphamide ,Hyper-CVAD ,Dasatinib ,Blastic Phase ,Philadelphia chromosome ,Gastroenterology ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Philadelphia Chromosome ,030212 general & internal medicine ,business.industry ,Myeloid leukemia ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Transplantation ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Background Dasatinib monotherapy has demonstrated modest clinical activity in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP). The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has dramatically improved with hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with tyrosine kinase inhibitors (TKIs). Methods The authors reviewed 85 patients (23 with CML-LBP and 62 with newly diagnosed Ph-positive ALL) who received hyper-CVAD plus dasatinib. Results In the CML-LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML-LBP. The BCR-ABL1 transcript was p210 in 22 patients (96%) and p190 in 1 patient (4%). In the Ph-positive ALL cohort, p210 and p190 transcripts were detected in 13 patients (21%) and 48 patients (77%), respectively. Patients with CML-LBP were less likely to achieve deep molecular remission than patients with Ph-positive ALL: the major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). Survival outcomes were similar for CML-LBP and Ph-positive ALL: the 5-year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML-LBP (5-year OS rate, 88% vs 57%; P = .04). In Ph-positive ALL, the outcome was driven by deeper molecular remission: the 5-year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Conclusions The outcome of CML-LBP has improved with hyper-CVAD plus dasatinib therapy with survival comparable to that of Ph-positive ALL. Further improvement may be achieved with the use of novel TKIs and targeted agents.
- Published
- 2021
25. Azacytidine for the treatment of retrospective analysis from the Gruppo Laziale for the study of Ph-negative MPN.
- Author
-
Andriani, Alessandro, Montanaro, Marco, Voso, Maria Teresa, Villivà, Nicoletta, Ciccone, Fabrizio, Andrizzi, Cristina, De Gregoris, Cinzia, Di Veroli, Ambra, Maurillo, Luca, Alimena, Giuliana, and Latagliata, Roberto
- Subjects
- *
MYELOPROLIFERATIVE neoplasms , *AZACITIDINE , *LUNG infections , *RESPIRATORY insufficiency , *DRUG efficacy , *DISEASE progression , *THERAPEUTICS - Abstract
To highlight the role of azacytidine (AZA) in patients with myeloproliferative neoplasms developing blast phase (MPN-BP), we evaluated retrospectively 19 patients [M/F 15/4, median age 71.3 years, interquartile range (IQR) 64.5–77.7] reported in the database of our cooperative group. Median time from diagnosis to BP evolution was 52.7 months (IQR 11.2–181.8). All patients were treated with AZA at the standard dosage of 75 mg/m 2 . Two patients died early after 5-AZA initiation from pulmonary fungal infection and respiratory failure respectively, 4 patients had a disease progression, 4 patients a stable disease, 3 patients had an hematological improvement, 1 patient a partial response and 5 pts (26.3%) a complete response (CR) after 4, 4, 4, 5, and 12 months. The median cumulative survival from BP evolution was 9.9 months (95%CI 6.6–13.1): the comparison with an historical cohort of 72 patients with MPN-BP treated with approaches other than AZA (median cumulative survival 3.1 months, 95%CI 1.1–5.0) showed a significant advantage for patients treated with AZA ( p = 0.02). Our data confirm the relative efficacy and safety of AZA in this group of patients with otherwise dismal prognosis, underlining the possible achievement of long-lasting responses in a sizeable portion of them. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
26. THERAPEUTICAL APPROACH AND PROGNOSTIC FACTORS IN CHRONIC MYELOID LEUKEMIA.
- Author
-
Oana, Patrinoiu
- Subjects
- *
CHRONIC myeloid leukemia , *PROTEIN-tyrosine kinase inhibitors , *CANCER , *CYTOGENETICS , *PATIENTS - Abstract
Chronic myeloid leukemia is one of the most studied malignancy and also a very successful model of targeted oral therapy in cancer. Over the last decade, the majority of chronic phase CML patients treated with tyrosine kinase inhibitors (TKIs) enjoy excellent overall survival and disease-free survival. In the TKI era, complete cytogenetic response (CCyR) stands firmly as a response milestone affording critical protection against transforming disease. The odds of CCyR (0 Ph+ metaphases) at 12 or 18 month of treatment are lower for patients with higher Sokal risk score but once achieved it improves outcome. Also, a small increase of BCR-ABL transcript level at patients that achieved and maintain CCyR does not necessarily mean a change of therapy but a more careful follow-up. Allo-HSCT remains a vital therapeutic approach for patients with CP-CML that fail TKIs treatment and also for those diagnosed in a more advanced phase of disease. [ABSTRACT FROM AUTHOR]
- Published
- 2014
27. The role of molecular genetics in medical oncology
- Author
-
Freireich, E. J., Banzet, P., editor, Holland, J. F., editor, Khayat, D., editor, and Weil, M., editor
- Published
- 1994
- Full Text
- View/download PDF
28. Outcome of allogeneic haematopoietic stem cell transplantation in myeloproliferative neoplasm, unclassifiable: a retrospective study by the Chronic Malignancies Working Party of the EBMT
- Author
-
Sonja Martin, Donald Bunjes, Yves Chalandon, Vittoria Malpassuti, Donal P. McLornan, Andreas Neubauer, Nicolaus Kröger, Ibrahim Yakoub-Agha, Fabio Ciceri, Simona Iacobelli, Patrick Hayden, Martin Gramatski, Gerald Wulf, Martin Bornhäuser, Aleksandar Radujkovic, Blandine Guffroy, Dietrich W. Beelen, Juan Carlos Hernandez Boluda, Ernst Holler, Tomasz Czerw, Marie Robin, Victoria Potter, Anne Lippinkhof-Kozijn, Jan-Erik Johansson, Henrik Sengeloev, and Jakob Passweg
- Subjects
Male ,Transplantation Conditioning ,Databases, Factual ,Constitutional symptoms ,Medizin ,Disease ,Kaplan-Meier Estimate ,0302 clinical medicine ,conditioning ,Recurrence ,hemic and lymphatic diseases ,myeloproliferative neoplasms unclassifiable ,ddc:616 ,Incidence ,Hematopoietic Stem Cell Transplantation ,food and beverages ,Hematology ,Middle Aged ,Settore MED/01 ,Treatment Outcome ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,Adult ,Risk ,Societies, Scientific ,medicine.medical_specialty ,Blastic Phase ,Asymptomatic ,03 medical and health sciences ,Young Adult ,non-relapse mortality ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Myeloproliferative neoplasm ,Aged ,Retrospective Studies ,allogeneic stem cell transplant ,Myeloproliferative Disorders ,Thrombocytosis ,business.industry ,Retrospective cohort study ,medicine.disease ,Settore MED/15 ,Transplantation ,Mutation ,business ,030215 immunology ,Follow-Up Studies - Abstract
Myeloproliferative Neoplasm (MPN), unclassifiable (MPN-U) is a heterogeneous disease with regards to both clinical phenotype and disease course. Patients may initially be asymptomatic or present with leucocytosis or thrombocytosis, anaemia, progressive splenomegaly, constitutional symptom, thromboses or accelerated/blastic phase disease. Treatment strategies are variable and there are no widely accepted consensus management guidelines for MNU-U. Allogeneic Haematopoietic Cell Transplantation (allo-HCT) remains the only curative strategy yet outcomes, to date, are not well defined. We hereby report on the largest retrospective study of patients with MPN-U undergoing allo-HCT, highlighting the potentially curative role and providing clinicians with robust engraftment, GvHD and outcome data to facilitate patient discussion.
- Published
- 2020
29. Regulation of miR-126 and miR-122 Expression and Response of Imatinib Treatment on Its Expression in Chronic Myeloid Leukemia Patients
- Author
-
Sameer Ahmad Guru, Irfan Ahmad, Aliya Rizvi, Amit Kumar Verma, Mirza Masroor Ali Beg, Yamini Goyal, Saleh Mohammed Abdullah, and Juheb Akhter
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Myeloid leukemia ,Imatinib ,Antineoplastic Agents ,Hematology ,Disease ,Blastic Phase ,Imatinib treatment ,Fold change ,MicroRNAs ,Drug Resistance, Neoplasm ,hemic and lymphatic diseases ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,microRNA ,MiR-122 ,medicine ,Imatinib Mesylate ,Humans ,medicine.drug - Abstract
Background: MicroRNAs (miRNAs) have been observed to exhibit altered expression patterns in chronic myeloid leukemia (CML). Therefore, this study was aimed to evaluate the clinical importance of miR-126 and miR-122 expression in concert to imatinib response in CML patients. Methods: The present study included 100 CML and 100 healthy subjects. The expression of the 2 miRNAs was performed using TaqMan probe chemistry, and snU6 was used as internal control. Results: The expression of miR-126 and miR-122 was downregulated in CML patients, with a mean fold change ± SD 0.20 ± 0.33 and 0.22 ± 0.37, respectively. While the expression of both miRNAs was analysed before and after imatinib treatment, it was observed that the expression levels of both were increased after imatinib treatment by 26.25-fold (5.33 against 0.20) and 13.95-fold (3.07 against 0.22) and the increase was statistically significant (p < 0.0001 and p < 0.0001, respectively). The expression of miR-126 was not conclusive when compared in different clinical stages of the CML disease as it showed a decreased expression in patients with accelerated phase compared to chronic phase (mean fold change = 0.03 and 0.27, respectively), but patients with chronic phase and blastic phase had comparable expression (mean fold change = 0.27 and 0.24, respectively). We also observed an increased expression of both miRNAs after imatinib therapy in each clinical phase. Conclusion: The study concludes that expression of miR-126 and miR-122 increases after imatinib treatment in CML patients and that miR-126 defines the good responders of imatinib therapy.
- Published
- 2020
30. Outcomes of Chronic Phase Chronic Myeloid Leukemia after Treatment with Multiple Tyrosine Kinase Inhibitors
- Author
-
Angela Hatcher, Elliott F. Winton, Fuad El-Rassi, Jessica Neely, Vamsi Kota, Meena Joseph, Jee Hyun Kong, Jean Khoury, Martha Arellano, Leonard T. Heffner, Brittany Hill, Manila Gaddh, and Audrey S Kim
- Subjects
Oncology ,medicine.medical_specialty ,Myeloid ,medicine.drug_class ,lcsh:Medicine ,Blastic Phase ,Article ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,tyrosine kinase inhibitor ,chronic myeloid leukemia ,hemic and lymphatic diseases ,Internal medicine ,medicine ,chronic phase ,treatment-free remission ,business.industry ,lcsh:R ,Myeloid leukemia ,General Medicine ,Chronic phase chronic myeloid leukemia ,Discontinuation ,respiratory tract diseases ,medicine.anatomical_structure ,survival rates ,030220 oncology & carcinogenesis ,business ,Tyrosine kinase ,After treatment ,030215 immunology - Abstract
We sought to evaluate the outcomes of chronic phase (CP) chronic myeloid leukemia (CML) in an era where five tyrosine kinase inhibitors (TKIs) are commercially available for the treatment of CML. Records of patients diagnosed with CP CML, treated with TKIs and referred to our center were reviewed. Between January 2005 and April 2016, 206 patients were followed for a median of 48.8 (1.4&ndash, 190.1) months. A total of 76 (37%) patients received one TKI, 73 (35%) received two TKIs and 57 (28%) were exposed to >, 3 TKIs (3 TKIs, n = 33, 4 TKIs, n = 17, 5 TKIs, n = 7). Nineteen (9.2%) patients progressed to advanced phases of CML (accelerated phase, n = 6, myeloid blastic phase, n = 4, lymphoid blastic phase, n = 9). One third (n = 69) achieved complete molecular response (CMR) at first-line treatment. An additional 55 patients achieved CMR after second-line treatment. Twenty-five patients (12.1%) attempted TKI discontinuation and 14 (6.8%) stopped TKIs for a median of 6.3 months (range 1&ndash, 53.4). The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs). The best OS was observed in patients tolerating and responding to first line TKI, but multiple TKIs led patients to gain treatment-free remission.
- Published
- 2020
31. Chronic Myeloid Leukemia Prognosis and Therapy: Criticisms and Perspectives
- Author
-
José Valentín Garcia-Gutierrez, Domenico Russo, Simona Soverini, Michele Baccarani, Russo, Domenico, Garcia-Gutierrez, José Valentín, Soverini, Simona, and Baccarani, Michele
- Subjects
Oncology ,MRD monitoring ,NGS mutation ,digital PCR ,prognosis ,quantitative PCR ,therapy guidelines ,treatment de-escalation ,treatment free remission ,tyrosine kinase inhibitor ,medicine.medical_specialty ,medicine.drug_class ,Population ,Clone (cell biology) ,lcsh:Medicine ,Blastic Phase ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,education ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,business.industry ,lcsh:R ,Myeloid leukemia ,General Medicine ,Transplantation ,Haematopoiesis ,Editorial ,030220 oncology & carcinogenesis ,therapy guideline ,Stem cell ,business ,prognosi - Abstract
Ph+ chronic myeloid leukemia (CML) is a clonal myeloproliferative disease whose clinical course is characterized by progression disease from the early chronic phase (CP) to the fatal blastic phase (BP). This programmed course is closely related to the translocation t(9;22)(q22;q11) and the resulting BCR-ABL1 fusion protein (p210) that drives the leukemic transformation of hematopoietic stem cells. Therefore, the cure of CML can only pass through the abrogation of the Ph+ clone. Allogeneic stem cell transplantation (allo-SCT) and interferon-alpha (IFNα) have been proven to reduce the Ph+ clone in a limited proportion of CML population and this translated in a lower rate of progression to BP and in a significant prolongation of survival. Tyrosine-kinase inhibitors (TKIs), lastly introduced in 2000, by preventing the disease blastic transformation and significantly prolonging the survival in up to 90% of the patient population, radically changed the fate of CML. The current therapy with TKIs induces a chronicization of the disease but several criticisms still persist, and the most relevant one is the sustainability of long-term therapy with TKIs in terms of compliance, toxicity and costs. The perspectives concern the optimization of therapy according to the age, the risk of disease, the potency and the safety profiles of the TKIs. The prolongation of survival is the most important end point which should be guaranteed to all patients. The treatment free remission (TFR) is the new goal that we would like to give to an increasing number of patients. The cure remains the main objective of CML therapy.
- Published
- 2020
32. Abstract 3117: CD80 can be the marker of chronic myeloid leukemia stem cells and regulated by BCR-ABL signaling
- Author
-
Chenyang Zhang, Miyuki Azuma, Huixin Li, Satoru Aoyama, Yohei Kawano, Shunichiro Yasuda, and Norihiko Kawamata
- Subjects
Cancer Research ,biology ,Myeloid leukemia ,chemical and pharmacologic phenomena ,Blastic Phase ,medicine.anatomical_structure ,Oncology ,hemic and lymphatic diseases ,biology.protein ,Cancer research ,medicine ,Bone marrow ,Kinase activity ,Antibody ,Stem cell ,CD80 ,K562 cells - Abstract
Chronic myeloid leukemia (CML) is a hematological malignancy caused by an abnormal tyrosine kinase, BCR-ABL1. Leukemic stem cells (LSCs) in this disease proliferate indefinitely. Also, the LSCs normally differentiate into mature neutrophils. Although tyrosine kinase inhibitors (TKIs) that target the kinase activity of BCR-ABL1 improved prognosis of CML patients, many patients still have residual diseases and need life-long treatment with the TKIs. This is due to a small number of CML LSCs that cannot be completely eradicated by the TKIs. It has been hypothesized that not only chemotherapy alone, but also immune surveillance systems of patients are needed to completely eradicate cancerous cells from their body. We hypothesized that residual CML cells might escape from the immune surveillance. Surfaces molecules associated with immune surveillance are examined on CML cells. At first, we confirmed expression levels of CD80 and PD-L1 by flowcytometry using CML cell lines. Our data showed that CD80 was expressed on surfaces of CML derived cell, K562, not PD-L1. Moreover, an engineered K562 subline is generated with the constitutive active JAK2V617F gene and became dependent on JAK-STAT signaling, but not BCR-ABL. This subline did not show CD80 on the surface. The TKIs inhibited expression of CD80 on the parental K562. Meanwhile, an ERK inhibitor decreased CD80 expression in K562. These results suggested that CD80 was downstream of BCR-ABL-ERK signaling pathway, not JAK-STAT pathway. When K562 cells were differentiated into mature neutrophils by ATRA, levels of CD80 decreased. Cytotoxicity assays using K562 and NK cells from normal individuals showed that the parental K562 cells and K562 cells with decreased levels of CD80 were similarly killed. These data suggested that CD80 on K562 played a minimum role in NK cell immune surveillance. We also found that only a small fraction of CD11b positive monocytes in normal peripheral blood showed expression of CD80. Also, blastic cells of CML blastic phase showed CD80 expression. These results suggested that only blastic cells of CML and a fraction of monocytes expressed CD80. These cells were distinguished by expression of CD11b as a marker. Although it is currently impossible to distinguish normal stem cells from CML LSCs, our study suggested that CD80/CD11b might be helpful to distinguish the CML LSCs in patients' bone marrow. It may be possible to collect a very small number of CML LSCs in CML patients under the TKI treatment using these antibodies and characterize the residual LSCs. Citation Format: Huixin Li, Shunichiro Yasuda, Satoru Aoyama, Chenyang Zhang, Yohei Kawano, Miyuki Azuma, Norihiko Kawamata. CD80 can be the marker of chronic myeloid leukemia stem cells and regulated by BCR-ABL signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3117.
- Published
- 2021
33. Serum Lipidome and Glucose Metabolism Uncover Vulnerabilities in Myelodysplasia and Secondary Acute Myelogenous Leukemia
- Author
-
Rafee Talukder, Gustavo A. Rivero, and Samer Al Hadidi
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Secondary acute myelogenous leukemia ,Cell Biology ,Hematology ,Blastic Phase ,Lipidome ,Carbohydrate metabolism ,medicine.disease ,Biochemistry ,Gastroenterology ,chemistry.chemical_compound ,Leukemia ,chemistry ,Low-density lipoprotein ,Internal medicine ,medicine ,Hemoglobin ,business ,Lipoprotein - Abstract
Background Secondary acute myelogenous leukemia (sAML) is highly aggressive and molecularly heterogenous. Previous reports have demonstrated differential serum lipid expression among hemopoietic malignancies (i.e AML, myelodysplastic syndrome (MDS) and acute lymphoblastic leukemia (ALL). Such a distinct serum lipidome among hemopoietic disorders suggest "unique oncogenic metabolic addiction" of leukemia initiating cells (LICs). MDS to AML transition is characterized by clonal evolution [i.e severe aneuploidy, high P53 frequency etc.] and chemorefractoriness. However, mechanism(s) for transformation are not entirely understood. In this study, we investigate serum lipidome and "proxy" of glucose [HbA1C] metabolism among: (1) low risk, (2) high risk MDS and (3) sAML patients (pts) to identify features that may suggest disease specific vulnerabilities. Methods After IRB approval, 214 pts were selected for analysis. ANOVA was used to detect differential expression of total cholesterol (TC), low density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TAG) among low risk, high risk and sAML pts. Multivariate linear regression model was performed to evaluate the independent effect of confounders on relevant lipid modifications observed among subtypes of MDS and sAML pts. SAS software was used for data processing. Results 69/214 (32.2%), 26/214 (12.1%), 35/214 (16.3%), 35/214 (16.3%), 28/214 (13.08%), 21/214 (9.8%) were sAML, very low (VLR), low (LR), intermediate (I), high (H) and very high risk (VHR) MDS. Median age (range) was 68 y (42-91), 68 y (22-87), 70 y (55-91), 76 (53-88), 72 y (60-85) and 74 y (54-84), for sAML, VLR, LR, I, H and VHR, p=0.0001. In sAML, VLR, LR, I, HR and VHR MDS TC was 177 mg/dL, 150 mg/dL, 126 mg/dL, 134 mg/dL, 125 mg/dL and 122 mg/dL, p=0.0001; LDL was 113.4 mg/dL, 81.3 mg/dL, 67.8 mg/dL, 72 mg/dL, 63.2 mg/dL and 70.8 mg/dL, p=0.0001; HDL 35.8 mg/dL, 39.2 mg/dL, 36.1 mg/dL, 40 mg/dL, 33.7 mg/dL, 32.05 mg/dL, p=0.40; TAG 134 mg/dL, 140 mg/dL, 109 mg/dL, 120 , mg/dL 134 mg/dL, 98 mg/dL, p=0.1. Given "similarities" among MDS subgroups, "MDS lipid data" was compared vs sAML. Median TC, LDL, HDL and TAG among sAML vs MDS pts was 179.1 mg/dL vs 130.4 mg/dL, p=0.0001; 113 mg/dL vs 70.1 mg/dL, p=0.0001; 38.6 mg/dL vs 36.7 mg/dL, p=0.5; 142 mg/dL vs 116.6 mg/dL, p=0.056, respectively. 20/89 (22.7%) vs 69/89 (77.53%) sAML vs MDS pts, respectively were diabetic, p=0.002, OR =2.62; 95% CI 1.40-4.90. However, data extracted from 82 pts (16 sAML and 66 MDS, each) demonstrated that hemoglobin A1C (HbA1C) was 7.84% vs 6.34%, in sAML vs MDS, respectively, p=0.009. Multivariate linear regression accounting for age, blast count, BMI, DM status and HbA1C showed that higher TC, LDL and HbA1C were independent predictors of sAML. Conclusions While this study is restricted to demonstrate distinct lipid and metabolic profile between sAML and MDS, our results suggest blastic phase dependency on higher serum cholesterol and possibly higher advanced glycosylation. As compared to MDS, our data highlights the possibility that sAML induces serum Lipidome modifications that may "hijack endogenous lipogenesis" to favor TC, LDL and possibly TAG production. Additionally, despite larger number of patients is needed to confirm our results, higher HbA1C potentially initiates advanced glycosylation facilitating blastic conversion in MDS pts. Disclosures Rivero: Incyte: Membership on an entity's Board of Directors or advisory committees; agios: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees.
- Published
- 2020
34. A Multicenter Prospective Study on Efficacy and Safety of Ponatinib in Patients with Chronic Myeloid Leukemia Resistant or Intolerant to Previous Therapy: A 3-Year Report
- Author
-
Małgorzata Kopera, Ewa Medras, Renata Kasza, Aleksandra Kostyra, Anna Rudkowska-Kazanowska, Monika Joks, Ryszard Wichary, Edyta Paczkowska, Joanna Niesiobedzka-Krezel, Magdalena Swiniarska, R. Kroll-Balcerzak, Elżbieta Patkowska, Olga Grzybowska-Izydorczyk, Hanna Ciepluch, Elżbieta Szczepanek, Tomasz Sacha, Justyna Gil, Janusz Kloczko, Wioletta Makowska, Paulina Dumnicka, Marta Oller, Malgorzata Wach, Witold Prejzner, Grazyna Bober, Joanna Wasilewska, Joanna Gora-Tybor, Ewa Wasilewska, and Tomasz Gromek
- Subjects
medicine.medical_specialty ,Hematology ,business.industry ,Immunology ,Ponatinib ,Imatinib ,Cell Biology ,Blastic Phase ,Biochemistry ,Confidence interval ,chemistry.chemical_compound ,Blood pressure ,chemistry ,Internal medicine ,Toxicity ,Medicine ,business ,Prospective cohort study ,medicine.drug - Abstract
Introduction Tyrosine kinase inhibitors (TKIs) have transformed outcomes in chronic myeloid leukemia (CML). Patients who respond to imatinib, have a life expectancy comparable with that of the global population, however, up to 40% of patients discontinue imatinib due to resistance or intolerance. Ponatinib is a third-generation highly-potent-pan-inhibitor of tyrosine kinases, active in all single resistance ABL kinase mutations, including the T315l mutation. This report presents the results of a prospective analysis of 3-year ponatinib therapy available in Poland by Angelini's donation program for patients in all phases of CML resistant or intolerant to previous TKI therapy. Methods 43 CML patients (20 women, 24 men, aged 19 to 76 years, mean age 49 ± 15 years) were treated in 20 Polish Hematology Centers with ponatinib initiated between March 2016 and December 2019. 23 pts (53%) were in the chronic phase (CP), 3 pts (7%) in accelerated phase (AP), and 17 pts (40%) in blastic phase (BP) (9 myeloblastic and 8 lymphoblastic). The majority of patients received three lines of TKI therapy. The T315I mutation was detected in 30% of patients (the initial characteristics of the 43 analyzed patients are shown in Table 1). The indication for ponatinib and its dose schedule was made according to the discretion of the attending physician. The initial dose of ponatinib was 45 mg/d in 60% of all patients (without statistically significant differences in the initial dose between patients starting treatment in CP, AP, and BP). Molecular biology tests were performed according to ELN guidelines and BCR-ABL/ABL ratios were expressed as % [IS] in all patients. Treatment responses were calculated at each specific time points recommended by ELN. Statistica 12 software (StatSoft, Tulsa, OK, USA) was used for calculations. Results The follow-up ranged from one week to 35.4 months (median 11.4 months) (one male patient died on infection one week after ponatinib introduction and was excluded from further analysis, he did not achieve CHR and he transformed to blast phase-BP). The responses to ponatinib are shown in Table 2. Among 23 CP patients, 18 achieved CHR (78%), 6 (26%) MCyR, 5 (22%) CCyR, and 1 (4%) MMR at 1 month of treatment. There were only 2 patients in this group (9%) who did not achieve CHR. Eleven CP patients (48%) achieved stable MMR. In all 3 AP patients, the best responses (CHR, CCyR, and MMR) were maintained until the end of observation (Table 2). Among 17 BP patients, 8 (47%) achieved CHR. The overall survival was significantly better in those patients who achieved CHR at 1 month of therapy (Figure 1). 19 patients (44%) experienced toxicity of ponatinib including: increase in blood pressure overall 9 patients (21%), hematological toxicity grade 3-4- 12 patients (28%).A total of 19 patients (44%) remained on ponatinib at the end of the observation. Ponatinib dose was reduced during the study in 18 patients (42%): in 11 (61% of those requiring dose reduction) because of toxicity, in 6 (33%) because of good response to treatment, and in 1 patient (6%) because of both reasons. The need for dose reduction was not significantly associated with comorbidities (p=0.4). Eight patients (19%) underwent allo-SCT during the observation. Ponatinib was discontinued in eight patients (19%), in six CP and two BP-patients. In five patients (12%), ponatinib was discontinued because of toxicity (hematological in one, non-hematological in two, and both in one patient); all were CP patients. In two patients (one CP, one BP patient), ponatinib was discontinued as they underwent allo-SCT. Overall, 16 patients (37%) died during the study: 12 of them (28%) due to CML progression. In all 43 patients, median survival was not reached. The estimated 2-year survival was 60% (95% confidence interval 44-76%) (Figure 2A) 84% in CP patients, 100% in AP patients (Figure 2B), and 20% in BP patients. None of the CP patients progressed to AP or BP during the study, i.e. progression-free survival was 100% at the end of observation (35.4 months). The presence of T315I mutation (p=0.2) or the initial dose of ponatinib (p=0.4) was not significantly associated with the overall survival. Conclusion Our study confirmes that ponatinib could induce durable responses with acceptable toxicity profiles in highly pretreated patients with CML resistant or intolerant to previous TKIs treated in standard clinical practice. Disclosures Sacha: Adamed:Consultancy, Honoraria;Bristol-Myers Squibb Company:Consultancy, Honoraria, Speakers Bureau;Pfizer:Consultancy, Honoraria, Speakers Bureau;Novartis:Consultancy, Honoraria, Speakers Bureau;Incyte:Consultancy, Honoraria, Speakers Bureau.Niesiobedzka-Krezel:Angelini Pharma:Other: lecture fee and meeting partcipation.Ciepluch:Copernicus Wojewodzkie centrum Onkologii:Current Employment.
- Published
- 2020
35. Reverse phase protein array profiling reveals distinct proteomic signatures associated with chronic myeloid leukemia progression and with chronic phase in the CD34-positive compartment.
- Author
-
Quintás-Cardama, Alfonso, Qiu, Yi Hua, Post, Sean M., Zhang, Yiqun, Creighton, Chad J., Cortes, Jorge, and Kornblau, Steven M.
- Subjects
- *
PROTEIN microarrays , *PROTEOMICS , *CHRONIC myeloid leukemia , *CANCER invasiveness , *CD34 antigen , *PROTEIN-tyrosine kinases , *MONOCLONAL antibodies - Abstract
BACKGROUND: Chronic myeloid leukemia (CML) is a clonal stem cell malignancy whose pathogenesis is driven by constitutive activation of the breakpoint cluster region-v-abl Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) kinase. Although BCR-ABL1 activation is present in all patients with CML, patients can present in 3 different phases characterized by an increasingly worse prognosis and diminished responsiveness to tyrosine kinase inhibitors: chronic phase, accelerated phase, or blastic phase. The biologic basis for progression from chronic phase to blastic phase and for regulating the homeostasis of tyrosine kinase inhibitor-resistant CML stem cells is not entirely understood. METHODS: To shed some light into these aspects of CML biology, the authors used reverse phase protein arrays probed with 112 individual monoclonal antibodies to compare protein expression patterns in 40 samples of leukemia-enriched fractions from patients with CML (25 in chronic phase, 5 in accelerated phase, and 10 in phase). RESULTS: An analysis of variance (significance cutoff, P < .01) unveiled a set of proteins that were overexpressed in blastic phase, including heat-shock protein 90 (hsp90); retinoblastoma (Rb); apoptosis-inducing factor (AIF); serine/threonine-protein phosphatase 2A (PP2A); B-cell leukemia 2 (Bcl-2); X-linked inhibitor of apoptosis protein (Xiap); human homolog of Drosophila Mad (mothers against decapentaplegic) and related Caenorhabditis elegans gene Sma, family member 1 (Smad1); single-stranded DNA binding protein 2 alpha (SSBP2α); poly(adenosine diphosphate-ribose) polymerase (PARP); GRB2-associated binding protein 2 (Gab2); and tripartite motif containing 24 (Trim24). It is noteworthy that several of these proteins also were overexpressed in the CD34-positive compartment, which putatively contains the CML stem cell population. CONCLUSIONS: The results from this study indicated that reverse phase protein array analysis can unveil differentially expressed proteins in advanced phase CML that can be exploited therapeutically with targeted approaches. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
36. Treatment of Philadelphia-negative myeloproliferative neoplasms in accelerated/blastic phase with azacytidine. Clinical results and identification of prognostic factors
- Abstract
There have been some reports on a possible role of azacytidine (AZA) in the treatment of accelerated/blastic phase evolved from Philadelphia-negative myeloproliferative neoplasms (MPN-AP/BP), but results are conflicting. In this study, we analyzed a cohort of 39 patients with MPN-AP/BP treated frontline with AZA at the standard dosage (75 mg/m2). Median time from diagnosis to AP/BP evolution was 92.3 months (IR 29.9-180.1). All patients were evaluable for hematologic response: two patients (5.2%) died early after AZA initiation, 13 patients (33.3%) had a progressive or stable disease, nine (23.1%) had a hematologic improvement (HI), seven (17.9%) achieved a partial response (PR), and eight (20.5%) a complete response (CR). Overall, 24 patients achieved a clinical hematologic response (HI + PR + CR), with an overall response rate of 61.5%. Median overall survival (OS) from AZA start of the whole cohort was 13.5 months (95% CI, 8.2-18.7). There was no difference in median OS among patients with HI, PR, or CR (P =.908). These three subgroups as “responders” having been considered, a significantly better OS was observed in responder compared with nonresponder patients, with a median OS of 17.6 months (95% CI, 10.1-25.0) versus 4.1 months (95% CI, 0.4-10.0) (P =.001) Only female gender was significant for both achievement of response (.010) and OS duration (P =.002). In conclusion, AZA is useful for the management of MPN-AP/BP, with an overall response rate (HI + PR + CR) of 61.5% and a longer OS in responders.
- Published
- 2019
37. Sequential array comparative genomic hybridization analysis identifies copy number changes during blastic transformation of chronic myeloid leukemia
- Author
-
Lee, Seung-Tae, Ji, Yongick, Kim, Hee-Jin, Ki, Chang-Seok, Jung, Chul Won, Kim, Jong-Won, and Kim, Sun-Hee
- Subjects
- *
CHRONIC myeloid leukemia , *CANCER invasiveness , *CANCER genes , *GENE fusion , *CHROMOSOMES , *COMPARATIVE studies , *FOLLOW-up studies (Medicine) - Abstract
Abstract: The present study was performed to provide direct evidence on copy number changes during progression from chronic phase (CP) to blastic phase (BP) in chronic myeloid leukemia (CML) through a longitudinal follow-up study. Matched CP and BP samples in three patients were analyzed using high-resolution array comparative genomic hybridization (aCGH) chips. During blastic transformation, loss of large genomic segments including 6q14.1-q22.31, chromosome 7 and 9p13.2-p21.3 were noted. Furthermore, small-sized copy number changes involving cancer-associated genes were observed. In addition, we identified a novel fusion gene consisted of PAX5 and MLLT3 (AF9). It is likely that blastic transformation of CML is a multi-step process associated accumulation of several genomic events which may largely overlap with those found in acute leukemias. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
38. Synergistic interactions between 12-0-tetradecanoylphorbol-13-acetate (TPA) and imatinib in patients with chronic myeloid leukemia in blastic phase that is resistant to standard-dose imatinib
- Author
-
Fang, Baijun, Song, Yongping, Han, Zhengtao, Wei, Xudong, Lin, Quande, Zhu, Xiaoxiu, Yang, Ruyu, Sun, Junzhong, Tian, Guofeng, Liu, Xinjian, Cao, Guoshun, Shi, Yin, Nie, Neng, Li, Dapeng, and Zhao, Robert Chunhua
- Subjects
- *
VITAMIN D , *STEROID hormones , *IMATINIB , *PROTEIN-tyrosine kinase inhibitors - Abstract
Abstract: We have demonstrated that 12-0-tetradecanoylphorbol-13-acetate (TPA) combined with vitamin D3 (VD3) and cytosine arabinoside (Ara C) is effective and feasible for chronic myelogenous leukemia (CML) in blastic phase (BP). In the current study, the efficacy of TPA combined with inhibitor imatinib mesylate (imatinib) was investigated in patients with CML in BP that was resistant to standard-dose imatinib (400mg/day). The results suggested that TPA combined with imatinib (400mg/day) might overcome disease-poor response to conventional doses. So this approach deserves further evaluation as frontline therapy for newly diagnosed CML. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
39. Neuroendocrine tumor of cecum in patient treated with imatinib mesylate for blastic phase of chronic myeloid leukemia
- Author
-
Anamarija Kovač Peić, Božena Coha, Hrvoje Holik, and Sabina Novaković
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Pathology ,Side effect ,medicine.drug_class ,Antineoplastic Agents ,Cecal Neoplasms ,Blastic Phase ,Gastroenterology ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,Ascites ,medicine ,Humans ,tyrosine kinase inhibitor ,secondary malignancy ,ascites ,Myeloproliferative disease ,Adverse effect ,Aged ,business.industry ,Myeloid leukemia ,Neoplasms, Second Primary ,Imatinib ,General Medicine ,Neuroendocrine Tumors ,030104 developmental biology ,Imatinib mesylate ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Imatinib mesylate (IM), a tyrosine kinase inhibitor, is the treatment of choice in patients with chronic myeloid leukemia (CML). It is considered a very safe drug, with mostly mild and reversible side effects. Lately, it has been suggested that adverse events may occur after a long term. We report a case of a 72-year-old woman diagnosed with blastic phase of Philadelphia chromosome positive CML treated with IM for 28 months. The patient presented first with ascites as a side effect of the drug. When the ascites re- occurred, it was caused by neuroendocrine tumor (NET) with peritoneal carcinomatosis. We believe this is the first case of a NET as a secondary malignancy (SM) after IM treatment. SM have been described in patients on IM before. It is unclear whether these tumors are caused by imatinib or found more easily because of close follow-up.
- Published
- 2017
40. Bosutinib as a fourth-line therapy for a patient with T315I-positive lymphoid blastic phase chronic myeloid leukemia: A case report
- Author
-
Yutaka Yatomi, Tomiko Ryu, Yuko Iwata, Kuniko Iihara, Shuichi Taniguchi, Hideki Uryu, Yumiko Satoh, Yukiko Komeno, Naoyuki Uchida, and Akiko Masuda
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Vincristine ,bosutinib ,Biology ,Blastic Phase ,T315I mutation ,03 medical and health sciences ,tyrosine kinase inhibitor ,0302 clinical medicine ,chronic myeloid leukemia ,hemic and lymphatic diseases ,Internal medicine ,medicine ,blastic phase ,Myeloid leukemia ,Articles ,medicine.disease ,Transplantation ,Dasatinib ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Bone marrow ,Bosutinib ,030215 immunology ,medicine.drug - Abstract
A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper-cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir. Bone marrow (BM) aspiration and biopsy revealed hypercellular marrow filled with blasts. Sequencing of the leukemia cells revealed overlapping peaks for the wild-type sequence and the T315I mutant sequence. The patient was treated with 500 mg bosutinib (which was later reduced to 300 mg) for pretransplant cytoreduction. After 5 months, the patient's spleen exhibited a reduction in volume and the percentage of blasts in the BM decreased from 96.1 to 17.5%. The patient successfully underwent cord blood transplantation. The patient has been disease-free for 5 months subsequent to transplantation. This case suggests that bosutinib may be effective for cytoreduction prior to stem cell transplantation, unless the leukemia cells consistently harbor the T315I mutation.
- Published
- 2017
41. Current approach to the treatment of chronic myeloid leukaemia
- Author
-
Ivan Pasic and Jeffrey H. Lipton
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents ,Blastic Phase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Hematologist ,Protein Kinase Inhibitors ,business.industry ,Ponatinib ,Imatinib ,Hematology ,Dasatinib ,030104 developmental biology ,chemistry ,Nilotinib ,030220 oncology & carcinogenesis ,Immunology ,business ,Bosutinib ,Tyrosine kinase ,Stem Cell Transplantation ,medicine.drug - Abstract
Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual. The treatment of CML has migrated in many jurisdictions from the office of a highly specialized malignant hematologist to the general hematologist or even a general practitioner. The goal of this review is to offer an overview of the modern approach to the treatment of CML, with an emphasis on chronic phase (CP) CML, including both TKI-based therapies such as imatinib, dasatinib, nilotinib, bosutinib and ponatinib, and non-TKI medications, such as omacetaxine. We discuss evidence behind each drug, most common and material adverse reactions and outline how this information can be used in selecting the right drug for the right patient. We also discuss evidence as it relates to other therapies, including stem cell transplant (SCT), and patients in accelerated (AP) and blastic phase (BP).
- Published
- 2017
42. Central Nervous System Relapse in Two Patients with Chronic Myelogenous Leukemia in Myeloid Blastic Phase on Imatinib Mesylate Therapy.
- Author
-
Rytting, Michaele E. and Wierda, William G.
- Subjects
- *
CENTRAL nervous system diseases , *MYELOID leukemia , *IMATINIB , *CEREBROSPINAL fluid , *DRUG therapy , *ANTINEOPLASTIC agents , *LYMPHOMAS - Abstract
We report two patients with Philadelphia (Ph) chromosome positive chronic myelogenous leukemia (CML) in myeloid blastic phase that developed central nervous system disease while on imatinib mesylate therapy. Patient 1 presented with CML in myeloid blastic phase and responded to imatinib, cytarabine, and idarubicin-based treatment achieving complete cytogenetic remission in the marrow, but developed myeloid blasts in his cerebrospinal fluid (CSF) during treatment. Patient 2 developed CML myeloid blastic phase after initially being in hematologic and cytogenetic remission with imatinib treatment. He represented with an extramedullary mass at the base of his skull and CSF involvement. Both patients were treated with intrathecal chemotherapy and received craniospinal irradiation to clear the spinal fluid of disease. Both patients have undergone related allogeneic stem cell transplant and are in complete hematologic remission; one is in complete cytogenetic remission, the other is too early to evaluate. Central nervous system involvement with myeloid blasts is previously unreported for patients with CML in blastic phase on imatinib and warrants cautious observation and vigilance in these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
43. Melphalan treatment in patients with myelofibrosis with myeloid metaplasia.
- Author
-
Petti, M. C, Latagliata, R, Spadea, T, Spadea, A, Montefusco, E, Aloe Spiriti, M. A, Avvisati, G, Breccia, M, Pescarmona, E, and Mandelli, F
- Subjects
- *
MYELOFIBROSIS , *MYELOID metaplasia , *THERAPEUTICS - Abstract
Summary. Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement > 5 cm and/or transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count > 20 × 109 /l and/or platelets > 1·0 × 109 /l] received low-dose Melphalan (2·5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66·7%) achieved a response after a median time of 6·7 months: 26 (26·3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40·4%) showed an improvement > 50% (partial response, PR). Thirty-three patients (33·3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28·4 and 26 months respectively: median survival of CR + PR patients was 71·2 months (95%CI: 33·8–108·7) versus 36·5 months (95%CI: 24·5–48·5) for the non-responders (log-rank test, P = 0·002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2·7], WBC count > 20 × 109 /l (HR = 2·4) and not achieving any type of response, either partial or complete (HR = 3·9). In conclusion, Melphalan could be a promising first-line option for MMM patients with clinical or haematological symptoms requiring treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
44. Treatment of blastic phase chronic myeloid leukemia with mitoxantrone, cytosine arabinoside and high dose methylprednisolone.
- Author
-
Bolaman, Zahit, Köseoglu, Mehmet, Ayyildiz, Orhan, Kadiköylü, Gürhan, Sönmez, Hulki Meltem, Demir, Süleyman, and Müftüoglu, Ekrem
- Subjects
- *
LEUKEMIA , *GLUCOCORTICOIDS , *DRUG therapy , *CHROMOSOMES - Abstract
Fourteen patients with blastic phase chronic myelogenous leukemia received combination chemotherapy with mitoxantrone 5 mg/m[sup 2] intravenously daily for 3 days, cytosine arabinoside 100 mg/m[sup 2] intravenously over 2 hours bid for 7 days and high dose methylprednisolone 1000 mg/day intravenously for 5 days. The patients' mean age was 52 ± 10 (range 34–64) and Philadelphia chromosome was positive in all. Five patients (35%) achieved complete remission and four patients (28%) had a partial remission. Overall remission rate was 64%. The mean survival was 11.1 ± 8.6 months (median 13) for all patients, 19.4 ± 4.0 months (median 19) for those achieving a complete remission, 12.50 ± 5.7 months (median 14) for patients with partial remission and 1.8 ± 1.8 months (median 2) for the unresponsive patients. Two of 5 unresponsive patients died early after the second course of remission induction. The treatment regimen was generally well tolerated. Marrow hypoplasia was observed in 9 (64%) patients and 7 (50%) had febrile episodes. Non-myelosupressive toxicity of the regimen was acceptable. Nausea and vomiting were observed in 8 (57%) patients and 3 (21%) patients developed flushing due to cytosine arabinoside. These results suggest that the regimen with mitoxantrone, cytosine arabinoside and high dose methylprednisolone in remission-induction of blastic phase chronic myelogenous leukemia may be a valid option that may also improve overall prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
45. Potential role of Wnt/β-catenin signaling in blastic transformation of chronic myeloid leukemia: cross talk between β-catenin and BCR-ABL
- Author
-
Hui Li, Yi Liu, Jing Hu, Min Feng, Zhenglan Huang, Zhang-ling Liu, and Wenli Feng
- Subjects
0301 basic medicine ,Chemistry ,Wnt signaling pathway ,Myeloid leukemia ,General Medicine ,Blastic Phase ,medicine.disease ,03 medical and health sciences ,Leukemia ,030104 developmental biology ,hemic and lymphatic diseases ,Immunology ,Cancer research ,medicine ,Kinase activity ,neoplasms ,Protein kinase B ,PI3K/AKT/mTOR pathway ,K562 cells - Abstract
Chronic myeloid leukemia (CML) results from malignant transformation of hematopoietic stem cells induced by the BCR-ABL oncogene. Transformation from chronic to blastic phase is the lethal step in CML. Leukemic stem cells (LSCs) are the basic reason for blastic transformation. It has been shown that Wnt/β-catenin signaling contributes to the self-renewal capacity and proliferation of LSCs in CML. However, the role of Wnt/β-catenin signaling in blastic transformation of CML is still obscure. Here, we explored the relationship between BCR-ABL and β-catenin signaling in vitro and in vivo. We found that BCR-ABL stimulated β-catenin via activation of PI3K/AKT signaling in blastic phase CML cells. Inhibition of the kinase activity of BCR-ABL, PI3K, or AKT decreased the level of β-catenin in both K562 cells and a CML mouse model and suppressed the transcription of downstream target genes (c-myc and cyclin D1). In addition, inhibition of the BCR-ABL/PI3K/AKT pathway delayed the disease progression in the CML mouse model. To further explore the role of β-catenin in the self-renewal and survival of CML LSCs, we established a secondary transplantation CML mouse model. Our data revealed that inhibition of the BCR-ABL/PI3K/AKT pathway reduced the tumor-initiating ability of K562 cells, decreased leukemia cell infiltration into peripheral blood and bone marrow, and prolonged the survival of mice. In conclusion, our data indicate a close relationship between β-catenin and BCR-ABL/PI3K/AKT in blastic phase CML. β-Catenin inhibition may be of therapeutic value by targeting LSCs in combination with a tyrosine kinase inhibitor, which may delay blastic transformation of CML.
- Published
- 2016
46. Resistance to imatinib in patients with chronic myelogenous leukemia and the splice variant BCR-ABL1 35INS
- Author
-
Wanlong Ma, Omar Abdel Wahab, Suresh C. Jhanwar, Cyrus V. Hedvat, Ellin Berman, Ross L. Levine, Maria E. Arcila, Molly Maloy, and Maher Albitar
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,RNA Splicing ,Blastic Phase ,Article ,Tyrosine-kinase inhibitor ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Treatment Failure ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,business.industry ,Kinase ,Point mutation ,Imatinib ,Sequence Analysis, DNA ,Hematology ,Middle Aged ,medicine.disease ,Mutagenesis, Insertional ,030104 developmental biology ,Protein kinase domain ,030220 oncology & carcinogenesis ,Immunology ,Imatinib Mesylate ,Mutation testing ,Female ,business ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Purpose In patients with chronic myelogenous leukemia (CML), point mutations in the BCR-ABL1 kinase domain are the most common cause of treatment failure with a tyrosine kinase inhibitor (TKI). It is not clear whether the splice variant BCR-ABL135INS is also associated with treatment failure. Patients and methods We reviewed all CML patients who had BCR-ABL1 kinase mutation analysis performed between August 1, 2007, and January 15, 2014. Patients who had BCR-ABL135INS detected had their medical records reviewed to determine response to TKI therapy. Results Two hundred and eighty four patients had kinase mutation testing performed; of these, 64 patients (23%) had BCR-ABL135INS detected. Forty-five patients were in chronic phase (70%), 10 were in accelerated phase (16%), 6 were in blastic phase (9%), and 3 were in other settings (5%). Of the 34 chronic phase patients who began therapy with imatinib, 23 patients (68%) failed therapy: 8 patients (24%) had primary refractory disease, 11 patients (32%) progressed, and 4 patients (12%) had disease progression after dose interruption. In contrast to the patients with disease progression or lack of response, none of 23 patients who were responding to imatinib had BCR-ABL135INS detected. DNA sequencing of commonly mutated spliceosomal genes SF3B1, U2AF1, SRSF2, ZRSR2, SFA31, PRPF408, U2A565, and SF1 did not reveal mutations in seven BCR-ABL135INS –positive patients tested. Conclusions The splice variant BCR-ABL135INS is frequently found in patients who are resistant to imatinib. Mutations in the commonly mutated spliceosomal proteins do not contribute to this association.
- Published
- 2016
47. Second chronic phase before transplantation is crucial for improving survival of blastic phase chronic myeloid leukaemia.
- Author
-
Visani, Giuseppe, Rosti, Gianantonio, Bandini, Giuseppe, Tosi, Patrizia, Isidori, Alessandro, Malagola, Michele, Stanzani, Marta, Martinelli, Giovanni, Piccaluga, Pierpaolo, Testoni, Nicoletta, Ricci, Paolo, and Tura, Sante
- Subjects
- *
MYELOID leukemia , *LEUKEMIA - Abstract
Because successful outcome after transplantation seems to depend in acute myeloid leukaemia (AML) and in chronic phase chronic myeloid leukaemia (CML) on disease status at the time of transplantation, we investigated whether FLAN (fludarabine, cytosine arabinoside, mitoxantrone) induction before allogeneic stem cell transplantation (allo-SCT) may be useful in blastic phase (BP)-CML. Twenty patients with BP-CML were studied: 10 patients received FLAN induction chemotherapy before proceeding to early allo-SCT, whereas 10 patients were submitted to bone marrow transplantation (BMT) without remission induction. Eight out of 10 (80%) patients achieved second chronic phase after one course of therapy with FLAN and seven patients (six in second chronic phase and one with partial response) were then submitted to allo-SCT. Of the six patients transplanted in the second chronic phase, all achieved molecular remission, four are still in second chronic phase, with intervals ranging from 10 to 54 months, whereas one patient died from infection having relapsed 14 months after SCT and one died of transplant-related complications in the second chronic phase. Mean durations of second chronic phase and survival after allo-SCT were both significantly longer than in the group of 10 BP-CML patients submitted to allo-SCT without FLAN remission induction treatment [22·4 (range 1–61) vs. 3·5 months (range 1–10) with FLAN and 22·7 (range 2–61) vs. 6·4 (range 1–16) months without FLAN]. We conclude that FLAN induction therapy followed by early allo-SCT appears to be effective in the treatment of BP-CML and could provide a curative possibility for BP-CML patients. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
48. Author response for 'Treatment of Philadelphia‐negative Myeloproliferative Neoplasms in Accelerated/Blastic Phase with Azacytidine. Clinical Results and Identification of Prognostic Factors'
- Author
-
Antonia Centra, Pasquale Niscola, Massimo Breccia, Luana Fianchi, Elena Maria Elli, Barbara Anaclerico, Roberto Latagliata, Roberto Foa, Ida Carmosino, Andrea Aroldi, Ambra Di Veroli, Nicoletta Villivà, Alessandro Andriani, Vincenza Martini, Guido Montanaro, Giulio Trapè, and Maria Teresa Voso
- Subjects
Philadelphia negative ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Identification (biology) ,Blastic Phase ,business - Published
- 2019
49. Review for 'Treatment of Philadelphia‐negative Myeloproliferative Neoplasms in Accelerated/Blastic Phase with Azacytidine. Clinical Results and Identification of Prognostic Factors'
- Author
-
Guido Ghilardi
- Subjects
Oncology ,Philadelphia negative ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Identification (biology) ,Blastic Phase ,business - Published
- 2019
50. Outcome of very elderly chronic myeloid leukaemia patients treated with imatinib frontline
- Author
-
Fabio Stagno, Patrizia Pregno, Alessandra Iurlo, Nicola Orofino, Gianfranco Giglio, Cristina Bucelli, Giovanna Mansueto, Massimiliano Bonifacio, Francesca Celesti, Elisabetta Abruzzese, Ester Orlandi, Antonella Russo-Rossi, Luigiana Luciano, Adam D'Addosio, Sara Galimberti, Dario Ferrero, Elena Crisà, Monica Crugnola, Gabriele Gugliotta, Enrico Montefusco, Gianantonio Rosti, Giovanna Rege Cambrin, Sergio Storti, Roberto Latagliata, Francesco Cavazzini, Fausto Castagnetti, Michele Cedrone, Mario Tiribelli, Endri Mauro, Antonella Gozzini, Gianni Binotto, Carmen Fava, Franca Falzetti, Mario Annunziata, Elisabetta Calistri, Romano Atelda, Federica Sorà, Nicola Sgherza, Isabella Capodanno, Sabina Russo, Malgorzata Monika Trawinska, Monica Bocchia, Massimo Breccia, Alessandro Isidori, Crugnola M., Castagnetti F., Breccia M., Ferrero D., Trawinska M.M., Abruzzese E., Annunziata M., Stagno F., Tiribelli M., Binotto G., Bonifacio M., Fava C., Iurlo A., Bucelli C., Mansueto G., Gozzini A., Falzetti F., Montefusco E., Crisa E., Gugliotta G., Russo S., Cedrone M., RussoRossi A., Pregno P., Isidori A., Mauro E., Atelda R., Giglio G., Celesti F., Sora F., Storti S., D'Addosio A., Galimberti S., Orlandi E., Calistri E., Bocchia M., Cavazzini F., Rege Cambrin G., Orofino N., Luciano L., Sgherza N., Rosti G., Latagliata R., and Capodanno I.
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Socio-culturale ,Tyrosine kinase inhibitor ,Blastic Phase ,Tyrosine-kinase inhibitor ,Chronic myeloid leukaemia, Elderly, Outcome, Tyrosine kinase inhibitor ,Chronic myeloid leukaemia ,Elderly ,Outcome ,Disease-Free Survival ,Follow-Up Studie ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,80 and over ,medicine ,Humans ,Chronic ,Survival rate ,Aged ,Aged, 80 and over ,Leukemia ,Hematology ,Settore MED/06 - ONCOLOGIA MEDICA ,business.industry ,Incidence (epidemiology) ,Imatinib ,General Medicine ,Survival Rate ,Female ,Follow-Up Studies ,Imatinib Mesylate ,030220 oncology & carcinogenesis ,Concomitant ,Toxicity ,BCR-ABL Positive ,business ,Myelogenous ,030215 immunology ,medicine.drug ,Human - Abstract
Very elderly (> 75years) chronic myeloid leukaemia (CML) patients at diagnosis are sometimes treated with different doses of imatinib (IM) based on concomitant diseases and physicians’ judgement. However, data on long-term follow-up of these patients are still lacking. To investigate treatment response and outcome, we retrospectively revised an Italian database of 263 very elderly CML patients receiving IM from the time of diagnosis. Median age at diagnosis was 78.5years and 56% of patients had 2 or 3 comorbidities. A complete haematological and cytogenetic response were achieved in 244 (92.8%) and 184 (69.9%) patients, respectively. In 148 cases (56.2%), a major molecular response was observed, which was deep in 63 cases (24%). A blastic phase occurred in 11 patients (4.2%). After a median follow-up of 45.0months, 93 patients have died (9 from disease progression) and 104 (39.5%) are still in treatment with IM. Incidence of grades 3–4 haematological and non-haematological toxicity was similar to those reported in younger patients. Five-year event-free survival was 54.5% and 45.2% in patients ≤80years and > 80years, respectively (p = 0.098). Five years OS was 75.7% and 61.6% in patients ≤80years and > 80years, respectively (p = 0.003). These findings show that IM plays an important role in frontline treatment of very elderly CML patients without increased toxicity and any effort to treat these patients with standard doses should be made in order to achieve responses as in younger subjects.
- Published
- 2019
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.