National Cancer Institute®
Last Modified: July 1, 2002
UI - 11972535
AU - Grainger JD; Will AM; Stevens RF
TI - Cultured autografting for juvenile myelomonocytic leukaemia.
SO - Br J Haematol 2002 May;117(2):477-9
AD - Royal Manchester Children's Hospital, Hospital Road, Pendlebury, Manchester M27 4HA, UK.
A case of juvenile myelomonocytic leukaemia (JMML) associated with a chromosomal translocation (1;5) is described. Initial cytoreductive therapy failed to control the disease. In the absence of a matched family or unrelated donor, a Dexter-type long-term bone marrow culture (LTBMC) was established. The LTBMC showed preferential growth of normal stem cells over the abnormal clone, allowing a cultured autologous stem cell transplantation to be performed. Despite detection of the t(1;5) from 5 months to 7 years following cultured autograft, the patient remained in haematological remission. Currently the patient is alive and well at 10 years in full cytogenetic remission.
UI - 11976825
AU - Hur M; Song EY; Kang SH; Shin DH; Kim JY; Park SS; Cho HI
TI - Lymphoid preponderance and the absence of basophilia and splenomegaly are frequent in m-bcr-positive chronic myelogenous leukemia.
SO - Ann Hematol 2002 Apr;81(4):219-23
AD - Department of Clinical Pathology, Seoul National University College of Medicine, Korea.
Chronic myelogenous leukemia (CML) with a minor bcr-abl transcript is a rare entity. We describe a 66-year-old female who was diagnosed with CML in the chronic phase. Molecular analysis of her Philadelphia chromosome using the reverse transcriptase polymerase chain reaction and subsequent sequencing revealed a minor bcr-abl transcript. Monocytosis resembling chronic myelomonocytic leukemia was observed without splenomegaly and basophilia. Her clinical course was indolent and maintained the chronic phase of CML for nearly 3 years under hydroxyurea treatment. A review of the 23 cases of m-bcr CML including this case showed the presence of monocytosis and the absence of basophilia and splenomegaly in 55.0%, 55.0%, and 70.0% of patients, respectively. The absence of basophilia was a significant finding in patients without monocytosis ( P=0.01). Although the hematological features or clinical outcomes were variable in m-bcr CML cases, all three cases at the onset of the blastic phase showed lymphoid crisis, implying an increased lymphoid leukemogenicity of minor bcr-abl transcripts.
UI - 11963764
AU - Hochhaus A; Berger U; Reiter A; Hehlmann R
TI - [Current pharmacotherapy of chronic myeloid leukemia]
SO - Internist (Berl) 2002 Feb;43(2):270-83
AD - III. Medizinische Universitatsklinik, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Wiesbadener Strasse 7-11, 68305 Mannheim.
UI - 12050948
AU - Hajek R; Koristek Z; Vinklarkova J; Janovska E; Klabusay M; Doubek M;
TI - Dvorakova D; Bourkova L; Dusek L; Buchler T; Adler J; Adam Z; Penka M; Mayer J; Vorlicek J Interleukin-2 activation of haematopoietic stem cells.
SO - Acta Med Austriaca 2002;29(2):61-7
AD - Department of Internal Medicine-Hematooncology, Department of Clinical Hematology, University Hospital Brno, Bohunice, Jihlavska 20, CZ-639 00 Brno, Czech Republic. firstname.lastname@example.org
BACKGROUND: Recent findings concerning the role of immunity in the eradication of residual malignant disease after autologous haematopoietic stem cell transplantation have led to extensive studies of T-cell and natural killer (NK) mediated anti-tumour effects. Interleukin 2 (IL-2) activation of autologous bone marrow (BM) or peripheral blood stem cells (PBSC) before transplantation is one of the methods of adoptive cell therapy. METHODS: Autologous BM of patients with chronic myelogenous leukaemia (n = 11) and PBSC of patients with multiple myeloma (n = 14) were activated by IL-2 in laboratory conditions with the aim of evaluating the feasibility of this method, the activation of T and NK cells, recovery of active progenitor cells, microbial contamination, and reduction of malignant cell content. RESULTS: Samples of BM (mean 2.6 x 10(6) cells) and PBSC (mean 10.3 x 10(6) cells) were cultured in complete culture medium with IL-2 (6000 Ul/ml) for 24 h. The recovery of CD34+ cells and CFU-GM was 82.5% and 51.5%, respectively, for BM, and 85% and 86%, respectively, for PBSC (mean values). No purging effect was detected by flow cytometry and a small decline in malignant cell contamination was observed by quantitative PCR in BM samples. No microbial contamination occurred during the sample processing. CONCLUSIONS: The described in vitro activation of BM and peripheral blood stem cells using IL-2 was evaluated as a safe and reliable method suitable for clinical application.
UI - 12057124
AU - Kurzrock R; Kantarjian H; Talpaz M
TI - Chronic myelogenous leukemia in chronic phase.
SO - Curr Treat Options Oncol 2001 Jun;2(3):245-52
AD - Department of Bioimmunotherapy, Box 422, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by genomic instability leading to its inevitable clinical evolution from an easily controlled chronic phase to a terminal blastic phase. The molecular abnormality responsible for this disease--BCR-ABL--and the critical biochemical aberrations resulting from it have been studied in depth. These discoveries have led to the development of a molecule, STI571, that specifically inhibits the abnormal kinase enzymatic activity exhibited by BCR-ABL. Early results of clinical trials using STI571 have shown responses even in blast crisis. There has also been striking hematologic and cytogenetic remission rates in patients with advanced chronic phase disease, with very little toxicity. It is our opinion that this molecule will revolutionize the treatment of CML. Furthermore, the path leading to its discovery will become a paradigm for cancer therapeutics. At the time of this writing, STI571 remains investigational (although it is widely believed that it will be approved for clinical use in the United States this year ). Although suggested therapy for a disease does not generally incorporate medications that are still investigational, in this case, the impact of a still investigational agent cannot be ignored. The current data suggest that STI571 will be the treatment of choice for patients with advanced or resistant chronic phase. To date, STI571 has not been studied adequately in untreated CML patients. Even so, it is our feeling that, based on its compelling success in patients with interferon-refractory and advanced disease and on its benign side effect profile, it will quickly become the front-line therapy for CML once it becomes available. Despite the ease of administration of STI571, patients should continue to be encouraged to participate in clinical studies so that several vital issues can be resolved: 1) the percentage of untreated CML patients who will eventually develop molecular remissions; 2) the proportion of patients in whom resistance to STI571 will emerge; 3) the optimum length of treatment; and 4) the impact on survival. Because interferon-alfa can also result in cytogenetic remissions, albeit in a small percent (less than 20%) of early chronic phase patients, it seems reasonable to suggest that patients who do not attain cytogenetic/molecular remissions with STI571 alone be treated with a combination of STI571 and interferon-alfa. Patients who are resistant to STI571 with or without interferon-alfa should undergo allogeneic hematopoietic cell transplant. Salvage therapy after transplant may include donor lymphocyte infusions, interferon-alfa, additional transplant, and perhaps STI571. Medications such as hydroxyurea appear destined to play a very limited role in CML. They may be used in the palliative treatment of older STI571-resistant patients or those without a transplant donor, although these patients may be best served by being considered for clinical trials of molecules, such as polyethylene glycol-interferon-alfa, on other novel agents.
UI - 12057067
AU - Bennett JM
TI - Chronic myelomonocytic leukemia.
SO - Curr Treat Options Oncol 2002 Jun;3(3):221-3
AD - University of Rochester Medical Center, James P. Wilmot Cancer Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA. email@example.com
Chronic myelomonocytic leukemia (CMML) has dysplastic and proliferative features. The median age of patients with CMML is 70 years; the median survival is approximately 2 years. Various chemotherapy regimens have been used with only modest success. When the proliferative phase prevails, hydroxyurea is the treatment of choice. For younger patients with high-risk CMML, an allogeneic bone marrow transplantation should be considered. If a donor cannot be identified, then combination acute myeloid leukemia-type therapy followed by an autologous stem cell or marrow transplant should be offered. Clinical trials should be considered if available because the overall results of therapeutic interventions are far from optimal.
UI - 11870247
AU - Savage DG; Antman KH
TI - Imatinib mesylate--a new oral targeted therapy.
SO - N Engl J Med 2002 Feb 28;346(9):683-93
AD - Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
UI - 12036887
AU - Huntly BJ; Bench AJ; Delabesse E; Reid AG; Li J; Scott MA; Campbell L;
TI - Byrne J; Pinto E; Brizard A; Niedermeiser D; Nacheva EP; Guilhot F; Deininger M; Green AR Derivative chromosome 9 deletions in chronic myeloid leukemia: poor prognosis is not associated with loss of ABL-BCR expression, elevated BCR-ABL levels, or karyotypic instability.
SO - Blood 2002 Jun 15;99(12):4547-53
AD - Department of Hematology, University of Cambridge, United Kingdom.
Deletions of the derivative chromosome 9 have recently been reported in chronic myeloid leukemia. These deletions are large, occur at the time of the Philadelphia (Ph) translocation, span the translocation breakpoint, and represent a powerful prognostic indicator. However, the molecular mechanisms responsible for the poor prognosis associated with deletions are obscure, and several possible models are investigated here. First, we demonstrate that all derivative chromosome 9 deletions detected by fluorescence in situ hybridization were associated with an absence of ABL-BCR expression. However, loss of ABL-BCR expression also occurred without an overt deletion, suggesting the existence of other mechanisms by which ABL-BCR transcription can be abolished. Furthermore, analysis of survival in 160 patients demonstrated that loss of ABL-BCR expression, in contrast to deletion status, was not an indicator of poor prognosis. Second, we addressed the possibility that concomitant small deletions of the Ph chromosome modulate BCR-ABL transcription. Real-time reverse-transcription polymerase chain reaction was used to demonstrate that derivative chromosome 9 deletions were not accompanied by altered levels of BCR-ABL transcripts. Third, deletions may represent a consequence of genetic instability within the target cell at the time of the Ph translocation, with the poor prognosis reflecting a predisposition to subsequent additional genetic alterations. However, patients with deletions do not exhibit an increased frequency of secondary cytogenetic changes following disease progression. Taken together, these data support a model in which deletions of the derivative chromosome 9 result in rapid disease progression as a result of the loss of one or more genes within the deleted region.
UI - 12028013
AU - Ranjitkumar S; Lindeman R
TI - Chronic myeloid leukaemia in megakaryocytic crisis.
SO - Br J Haematol 2002 Jun;117(3):487
AD - Prince of Wales Hospital, Randwick, NSW, Australia. firstname.lastname@example.org
UI - 12028029
AU - Numata A; Shimoda K; Gondo H; Kato K; Aoki K; Ito Y; Takase K; Asano Y;
TI - Okamura T; Niho Y; Harada M Therapy-related chronic myelogenous leukaemia following autologous stem cell transplantation for Ewing's sarcoma.
SO - Br J Haematol 2002 Jun;117(3):613-6
AD - Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-3-3 Maidashi, Higashi-ku, Fukuoka city, Fukuoka 812-8582, Japan.
A 17-year-old Japanese woman with Ewing's sarcoma was initially treated with conventional chemotherapy and local irradiation, and then with high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation. Four years later she was diagnosed with chronic myelogenous leukaemia (CML). The BCR/ABL fusion gene was detected in both peripheral blood and bone marrow cells by reverse transcription-polymerase chain reaction, but not in the harvest product of peripheral blood stem cells which were infused at the time of transplantation. This case adds to the accumulating evidence of therapy-related CML developing after high-dose chemotherapy and autologous stem cell transplantation.
UI - 12028032
AU - Petzer AL; Gunsilius E; Hayes M; Stockhammer G; Duba HC; Schneller F;
TI - Grunewald K; Poewe W; Gastl G Low concentrations of STI571 in the cerebrospinal fluid: a case report.
SO - Br J Haematol 2002 Jun;117(3):623-5
AD - Abteilung fur Hamatologie & Onkologie, Universitatsklinik Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. email@example.com
We report a 53-year-old man with lymphoid blast crisis of Ph+ chronic myeloid leukaemia who was treated with STI571, a selective inhibitor of the enzymatic activity of BCR-ABL. He responded excellently to STI571 (600 mg/d), obtaining a complete cytogenetic remission after 3 months of therapy. Although remission in the bone marrow was sustained, the patient developed an isolated central nervous system relapse. Subsequent analyses of STI571 concentrations in the cerebrospinal fluid (CSF) revealed 2-log lower CSF levels of STI571 than corresponding plasma levels. These are the first data demonstrating a low penetration of orally administered STI571 into the CSF in humans.
UI - 12028035
AU - Geiger TL; Woodard P; Tong X; Srivastava DK; Johnson R; Turner V; Hale
TI - G; Richardson S Human leucocyte antigen alloimmunization after bone marrow transplantation: an association with chronic myelogenous leukaemia.
SO - Br J Haematol 2002 Jun;117(3):634-41
AD - Department of Pathology, Mail Stop 341, St. Jude Children's Research Hospital, 132 North Lauderdale Street, Memphis, TN 38105-2794, USA. firstname.lastname@example.org
Platelet refractoriness due to human leucocyte antigen (HLA) alloimmunization is a significant risk to allogeneic bone marrow transplant recipients. To identify factors contributing to this risk, we reviewed the records of 317 consecutive, paediatric, allogeneic bone marrow transplant recipients at a single institution. The 6-year estimated cumulative incidence of platelet refractoriness due to HLA alloimmunization was 2.6% +/- 0.9%. The incidence among patients with chronic myelogenous leukaemia (CML) 12.5% +/- 5.3% was significantly greater than that of other patients (1.1% +/- 0.6%, P < 0.001). Graft rejection (P = 0.003) and the number of platelet transfusions during the first 90 d after bone marrow transplantation (BMT) (P = 0.0025) were also significantly associated with alloimmunization. The association with CML and with graft rejection was not seen among patients alloimmunized before transplantation. Eight patients developed alloimmunization, of whom three had mismatched grafts and four had unrelated grafts. Alloantibody specificities, identified in seven patients, were unrelated to host or graft major histocompatibility complex (MHC). Host recognition of alloantigens in transfused blood products, not graft-host recognition, therefore seems predominantly responsible for the alloimmunization. These results show that paediatric CML patients have a significantly increased risk of platelet refractoriness due to HLA alloimmunization after BMT. Identifying the mechanism for the increased alloimmunization risk may assist in the development of therapies to prevent platelet refractoriness.
UI - 11466696
AU - Giles FJ; Kantarjian HM; Kornblau SM; Thomas DA; Garcia-Manero G;
TI - Waddelow TA; David CL; Phan AT; Colburn DE; Rashid A; Estey EH Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation.
SO - Cancer 2001 Jul 15;92(2):406-13
AD - Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA. email@example.com
BACKGROUND: Mylotarg (Wyeth-Ayerst Laboratories, St. Davids, PA) is the brand name for a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab ozogamicin, CMA-676) and has been approved recently for the treatment of a subset of elderly patients who have relapsed acute myeloid leukemia (AML). Mylotarg is associated with an incidence of approximately 20% Grade 3 or 4 hyperbilirubinemia and liver transaminitis in this patient population. Hepatic venoocclusive disease (VOD) has been reported in patients who have undergone stem cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting, VOD has been associated very rarely with cytotoxic therapy. METHODS: The authors assessed the incidence of VOD in 119 patients who were receiving Mylotarg-containing non-SCT regimens. VOD was diagnosed through the use of standard Seattle and Baltimore criteria. RESULTS: A cohort of 119 (61 previously untreated, 58 with relapsed disease) patients with AML (92 patients), advanced myelodysplastic syndrome (25 patients), or chronic myeloid leukemia in blast phase (2 patients), received Mylotarg-based regimens. Fourteen (12%) developed VOD. The diagnosis of VOD was supported by histology in 2 patients and radiologic studies in a further 10 patients. Five (36%) of 14 patients with VOD had received no prior antileukemic cytotoxic therapy, including 2 patients who received single-agent Mylotarg therapy. CONCLUSIONS: Mylotarg was shown to be associated with the development of potentially fatal VOD in patients with leukemia who had not received SCT. VOD occurred when Mylotarg was used either as a single agent or when it was given with other cytotoxic agents. VOD occurred in Mylotarg-treated patients who had received no prior cytotoxic therapy. The current study concluded that risk factors for VOD should be assessed when considering Mylotarg therapy, and that attempts to avoid and treat VOD are warranted in patients who receive Mylotarg therapy. Copyright 2001 American Cancer Society.
UI - 12053151
AU - Ohsaka A; Hisa T
TI - Spectral karyotyping refined the identification of a der(Y)t(Y;1)(q11.1 or.2;q12) in the blast cells of a patient with atypical chronic myeloid leukemia.
SO - Acta Haematol 2002;107(4):224-9
AD - Department of Transfusion Medicine, Juntendo University School of Medicine, Tokyo, Japan. firstname.lastname@example.org
We report a case of atypical chronic myeloid leukemia who showed leukocytosis with immature granulocytes and dysplastic features but no monocytosis or basophilia. Cytogenetic analysis by conventional G-banding showed an abnormal clone, which was interpreted as 46,X,-Y,+der(?)t(?;1)(?;q?1), and no Philadelphia chromosome. Reverse transcription-polymerase chain reaction did not show either major or minor BCR-ABL chimeric mRNA. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) refined the karyotype to 46,X,der(Y)t(Y;1)(q11.1 or.2;q12). The der(Y)t(Y;1) abnormality was reported previously in 9 cases and associated with myelodysplastic syndrome or chronic myeloproliferative disorders. SKY in combination with the standard banding method and FISH may be useful for exploring undefined chromosome abnormalities in hematological disorders. Copyright 2002 S. Karger AG, Basel
UI - 11551022
AU - Deininger M; Ponisch W; Krahl R; Leiblein S; Edel E; Lange T; Fiedler F;
TI - Freund M; Franke A; Pasold R; von Grunhagen U; Herold M; Dolken G; Hoffmann FA; Uhle R; Schultze W; Steglich J; Schwarzer A; Richter P; Winkelmann C; Kettner E; Dachselt K; Subert R; Schwalbe E; Doepper J; Helbig W; Niederwieser D; East German Study Group Haematology/Oncology (OSHO) Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.
SO - Bone Marrow Transplant 2001 Jun;27(11):1125-32
AD - Department of Hematology, University of Leipzig, Germany.
Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.
UI - 11694412
AU - Billio A; Venturi R; Morello E; Rosanelli C; Pescosta N; Coser P
TI - Chronic neutrophilic leukemia evolving from polycythemia vera with multiple chromosome rearrangements: a case report.
SO - Haematologica 2001 Nov;86(11):1225-6
UI - 12075411
AU - Govender D; Pillay SV
TI - Mediastinal immature teratoma with yolk sac tumor and myelomonocytic leukemia associated with Klinefelter's syndrome.
SO - Int J Surg Pathol 2002 Apr;10(2):157-62
AD - Department of Pathology, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa.
A 14-year-old male presenting with a short history of right subclavicular chest pain was found to have a mediastinal tumor. Hematologic investigations and bone marrow examination showed features of myelomonocytic leukemia. The mediastinal tumor was excised, but the surgery was complicated by massive hemorrhage. The patient's condition deteriorated postoperatively and he died a week later. The histology of the mediastinal tumor showed the typical features of an immature teratoma with a yolk sac tumor. A prominent infiltrate of leukemic blast cells was present within blood vessels and in close proximity to the yolk sac component. The karyotypic analysis of leukemic cells isolated and cultured from the bone marrow showed 50XXY, +8, +21, +iso G-group marker chromosome karyotype.
UI - 11722980
AU - Druker BJ; Sawyers CL; Capdeville R; Ford JM; Baccarani M; Goldman JM
TI - Chronic myelogenous leukemia.
SO - Hematology (Am Soc Hematol Educ Program) 2001;():87-112
AD - Oregon Health and Science University, Portland, OR 97201-3098, USA.
The treatment recommendations for chronic myelogenous leukemia (CML) are evolving rapidly. In the past year, pegylated interferon and STI571 (Gleevec, imatinib mesylate), a Bcr-Abl tyrosine kinase inhibitor, have become commercially available and non-myeloablative stem cell transplants continue to be refined. Clinicians and patients face a bewildering array of treatment options for CML. In this article Dr. Sawyer reviews the clinical results with STI571 and ongoing investigations into mechanisms of resistance to STI571. Given the newness of STI571, a practical overview on the administration of STI571 is presented by Drs. Druker and Ford, focusing on aspects such as optimal dose, management of common side effects, and potential drug interactions. The most recent data on interferon-based regimens are reviewed by Dr. Baccarani in the third section. In the last section Dr. Goldman presents recent results of allogeneic stem cell transplants, including the reduced intensity conditioning regimens. Lastly, the proposed place of each of these treatments in the management of CML patients is addressed to assist in deciding amongst treatment options for CML patients.
UI - 12094245
AU - La Rosee P; O'Dwyer ME; Druker BJ
TI - Insights from pre-clinical studies for new combination treatment regimens with the Bcr-Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec) in chronic myelogenous leukemia: a translational perspective.
SO - Leukemia 2002 Jul;16(7):1213-9
AD - Oregon Health and Science University, Division of Hematology and Medical Oncology, Portland 97201, USA.
Clinical phase I/II studies with the Abl kinase inhibitor imatinib mesylate (Gleevec/Glivec, formerly STI571) for the treatment for chronic myelogenous leukemia (CML) demonstrated the safety and the remarkable efficacy of this molecularly targeted agent. However, a significant proportion of patients treated in the chronic phase of the disease after having failed interferon alpha (IFN) remain predominantly Philadelphia chromosome positive (Ph(+)), suggesting a risk of later relapses. Furthermore, results in blast crisis patients revealed a high frequency of relapses or resistance to imatinib. To circumvent resistance, improve response rates, or prolong survival, pre-clinical evaluations of combinations of imatinib with other agents have been pursued. Some of these have already been translated into clinical studies. Here, we first summarize evidence from pre-clinical studies on new combination regimens with imatinib in the treatment of CML. Second, we analyze preliminary clinical data of ongoing combination studies. Finally, we provide a summary of approaches that use novel antileukemic agents with molecularly characterized modes of action.
UI - 12094246
AU - Fischer T; Reifenrath C; Hess GR; Corsetti MT; Kreil S; Beck J;
TI - Meinhardt P; Beltrami G; Schuch B; Gschaidmeier H; Hehlmann R; Hochhaus A; Carella A; Huber C Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT).
SO - Leukemia 2002 Jul;16(7):1220-8
AD - 3 rd Medical Department, Johannes Gutenberg-University, Mainz, Germany.
We examined safety and efficacy of STI-571 in 24 bcr/abl-positive patients with CML post PBSCT. At start of STI-571 therapy, nine patients presented in blast crisis (BC) or in accelerated phase (AP), and 15 in chronic phase (CP). Patients were evaluated for hematologic, cytogenetic and molecular response, survival and toxicity. In general, STI-571 was well tolerated in this heavily pretreated group of patients with a non-hematologic and hematologic toxicity profile similar to that observed in a previous phase I trial at comparable doses. Five of nine patients with CML in transformation (AP, BC) were evaluable for hematologic response. Two of five patients had transient reductions in WBC and blasts, and three patients achieved a sustained hematologic response (>4 weeks). Cytogenetic analysis in these patients revealed numerical and/or structural responses. In CML chronic phase, STI-571 induced complete hematologic responses in all patients and major cytogenetic responses in 61% of patients with a complete cytogenetic response rate of 46%. This report indicates that STI-571 is a safe and effective drug in heavily pretreated patients. No apparent additional side-effects were noted in this patient cohort. The high rate of complete hematologic and complete cytogenetic responses in CP patients is remarkable, as intensive treatment approaches plus IFN-alpha failed to be efficient in achieving long-term stabilization of CML in this patient cohort.
UI - 12094265
AU - Andersen MK; Pedersen-Bjergaard J; Kjeldsen L; Dufva IH; Brondum-Nielsen
TI - K Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8.
SO - Leukemia 2002 Jul;16(7):1390-3
UI - 11426572
AU - Carella AM
TI - Mini-ice protocol is better than high-dose hydroxyurea to mobilize Ph-negative cells in earlier phases of chronic myelogenous leukemia.
SO - Leuk Lymphoma 2001 Jan;40(3-4):447-8
UI - 11899767
AU - Tennant L
TI - Chronic myelogenous leukemia: an overview.
SO - Clin J Oncol Nurs 2001 Sep-Oct;5(5):218-9
Important advances have been made in the treatment of chronic myelogenous leukemia (CML). In the past two decades, treatment of this disease has changed and now includes the use of hydroxyurea, interferon, tyrosine kinase inhibitors, and high-dose chemotherapy followed by hematopoietic stem cell transplantation. Because several relatively effective forms of therapy now exist, the care and management of patients with CML has become more complex. Through continued research and drug development, additional therapies are expected to emerge offering new hope and expanded treatment options for patients with CML.
UI - 11979553
AU - Loncarevic IF; Romer J; Starke H; Heller A; Bleck C; Ziegler M; Fiedler
TI - W; Liehr T; Clement JH; Claussen U Heterogenic molecular basis for loss of ABL1-BCR transcription: deletions in der(9)t(9;22) and variants of standard t(9;22) in BCR-ABL1-positive chronic myeloid leukemia.
SO - Genes Chromosomes Cancer 2002 Jun;34(2):193-200
AD - Institute for Human Genetics and Anthropology, FSU, Jena, Germany. email@example.com
The objective of this study was to characterize the ABL1-BCR fusion gene in 76 BCR-ABL1-positive chronic myeloid leukemia (CML) patients regarding expression as well as genomic status, to assess the frequency of ABL1-BCR gene deletion in these patients, which has been reported to be an adverse prognostic factor in Philadelphia chromosome-positive CML. Patients were analyzed for ABL1-BCR 1b-b3 and/or 1b-b4 transcription by RT-PCR analysis. ABL1-BCR gene status was analyzed by FISH in 16 CML patients with no ABL1-BCR transcript. FISH revealed a partial or total deletion of the ABL1-BCR gene in 9/16 and localized the 5' portion of ABL1 and the 3' portion of BCR at separated loci in 5/16 patients. The latter FISH pattern resulted from a nonreciprocal translocation in two and a complex translocation in three individuals. In 2/16 patients, FISH could not exclude an intact ABL1-BCR fusion gene. Thus, most CML patients without ABL1-BCR transcript could be characterized cytogenetically to belong to two major subgroups: a silent ABL1-BCR gene was attributed to a deletion in der(9)t(9;22) in 56% of the investigated patients or to variants of a standard t(9;22) (approximately 31%). Conversely, none of the 50 patients with an ABL1-BCR transcript exhibited a variant t(9;22) in GTG-banding analysis. Thus, genomic aberrations such as deletions or complex genomic rearrangements are the basic and most frequent cause for ABL1-BCR RNA negativity in CML. The heterogeneity of the underlying molecular mechanisms may explain divergent clinical implications described for patients with an ABL1-BCR deletion and those with no ABL1-BCR transcript. Copyright 2002 Wiley-Liss, Inc.
UI - 12057061
AU - Dutcher JP; Wiernik PH
TI - Accelerated and blastic phase of chronic myeloid leukemia.
SO - Curr Treat Options Oncol 2000 Apr;1(1):51-62
AD - Our Lady of Mercy Cancer Center/New York Medical College, 600 East 233rd Street, Bronx, NY 10466, USA.
There is currently no standard treatment for the blastic phase of chronic myeloid leukemia (CML-BC), which is a chemoresistant form of acute leukemia. Current approaches include using standard acute myeloid leukemia (AML) regimens in an effort to induce remission, variations of these approaches with drugs that seem more active in this specific leukemia, and the direct entry of patients into studies of investigational agents. Although the likelihood of achieving remission is small, immediate bone marrow transplantation in remission should be considered because it provides the only opportunity for long-term survival at this time. Allogeneic transplantation is preferred, but autologous transplantation of an early chronic phase marrow may provide benefit. Often, however, the duration of chemotherapy-induced remission of blast crisis is very short and may preclude entry into a transplant program. In addition, the patient may not be a candidate due to donor issues, age, or medical problems. If transplant is not an option, maintenance interferon is often used, although its benefit is uncertain. For patients in the accelerated phase of the disease, which is characterized by a variety of clinical presentations and cytogenetic abnormalities, the possibility of favorably manipulating the disease is greater. Again, there is no standard treatment, and clinical trials are recommended as first-line therapy. Treatment in the accelerated phase includes standard AML chemotherapy regimens, combinations of new agents, and the combination of cytostatic agents with interferon. Patients whose accelerated phase reverts to chronic phase after treatment may become candidates for bone marrow transplantation. However, current new approaches to the chronic phase applied in accelerated phase as well as new approaches directed specifically toward accelerated phase may lead to prolonged stabilization without bone marrow transplantation. In view of a median age of 55 at diagnosis of chronic phase, nontransplant regimens for accelerated phase that produce long-term benefit are urgently needed.
UI - 12088112
AU - Tothova E; Kafkova A; Stecova N; Fricova M; Guman T; Svorcova E
TI - Immune-mediated complications during interferon alpha therapy in chronic myelogenous leukemia.
SO - Neoplasma 2002;49(2):91-4
AD - Department of Hematology, Medical Faculty Hospital and UPJS Kosice, Slovak Republic. firstname.lastname@example.org
Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon alpha (IFNalpha) prolongs the survival by comparison with conventional chemotherapy. However, long-term treatment with Interferon alpha can produce or exacerbate immune-mediated complications (IMC). The purpose of this study was to analyze the experience with IMC in patients with chronic myelogenous leukemia (CML) undergoing IFNalpha treatment. The occurrence of IMC was evaluated in 76 patients (47 male; 29 female) with Philadelphia chromosome (Ph)-positive CML. Diagnostic criteria of IMC were performed in patients with symptoms suggestive of particular disorders. Well-documented and clinically evident complications developed in 7 patients after a median of 19 months (range 1-84) of IFNalpha treatment. These included 9.2% patients with Ph-positive CML treated with IFNalpha-containing regimens. Hypothyroidism (H) occurred in 1 patient (1.3%), immune-mediated hemolysis (HEM) in 2 patients (2.6%) and connective tissue disorders (CTD) in 4 patients (5.3%) (2 systemic lupus erythematosus--SLE, 1 Raynaud's phenomena and 1 mixed connective tissue disease--MCTD). IFNalpha was discontinued in 3 patients and the dose was reduced in 2 patients. Five of 7 patients (75%) with immune-mediated complications had some degree of cytogenetic response at the time of the event. The association with female sex was strong and significant (86% vs 33.6%, x2; 48; p = 0.02). The frequency of IMC of clinical relevance with interferon alpha therapy in CML increased (long-term therapy). The patients treated with interferon alpha should be monitored for signs and symptoms of autoimmunity.
UI - 12070006
AU - Sandlund JT; Harrison PL; Rivera G; Behm FG; Head D; Boyett J; Rubnitz
TI - JE; Gajjar A; Raimondi S; Ribeiro R; Hudson M; Relling M; Evans W; Pui CH Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia.
SO - Blood 2002 Jul 1;100(1):43-7
AD - Department of Hematology-Oncology, St Jude Children's Research Hospital, and the University of Tennessee, College of Medicine, Memphis, TN 38105, USA. email@example.com
We determined the prognostic importance of morphologically identifiable persistent disease at day 15 and days 22 to 25 of remission induction in childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2 consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations on day 15 (+/- 1 day) and 218 on days 22 to 25 (+/- 1 day). Fifty-seven patients (14%) had persistent lymphoblasts (> or = 1%) in the BM on day 15 and 27 patients (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free survival (EFS) was significantly worse for patients with lymphoblasts on day 15 (40% +/- 6%) or on days 22 to 25 (4% +/- 3%) as compared to those without lymphoblasts on these dates (78% +/- 2% and 76% +/- 2%, respectively, P <.001 for both comparisons). A worse prognosis was observed even for patients with a low percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS = 56% +/- 8%) or days 22 to 25 (5-year EFS = 0%) compared to those without morphologically identifiable persistent lymphoblasts at these times (P <.001 for both comparisons). The prognostic impact of persistent lymphoblasts on both dates remained significant after adjusting for other known risk factors, including treatment protocol, age, white blood cell count, DNA index, cell lineage, and central nervous system status, and National Cancer Institute/Rome criteria simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of remission induction was associated with a poor prognosis and on days 22 to 25 signified a particularly dismal outcome; these very high-risk patients require novel or more intensive therapy to improve outcome.
UI - 12111789
AU - Kataoka I; Shinagawa K; Shiro Y; Okamoto S; Watanabe R; Mori T; Ito D;
TI - Harada M Multiple sclerosis associated with interferon-alpha therapy for chronic myelogenous leukemia.
SO - Am J Hematol 2002 Jun;70(2):149-53
AD - Department of Internal Medicine II, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
We report a chronic myelogenous leukemia (CML) patient in chronic phase (CP) who developed multiple sclerosis (MS) in association with interferon-alpha (IFN-alpha) administration. In our patient, recombinant IFN-alpha2b therapy induced hematologically complete and cytogenetically major partial response for CML first, and sequential central nervous system dysfunction evolved, which subsided shortly after the cessation of its administration. Restarting IFN-alpha therapy by changing to a natural type of IFN-alpha resulted in rapid exacerbation of MS. The patient's neurological symptoms progressed gradually, but partial hematologic response persisted without any IFN-alpha derivatives or anti-cancer agents until a matched unrelated donor transplant procedure was performed. Myeloablative therapy led to lasting stable state of MS and finally to complete cytogenetic remission of CML. This patient's presenting clinical course and laboratory data suggest that both exertion of anti-leukemic activity and autoimmune process of MS might be mediated by mutual mechanisms, such as enhancement of specific cellular immunity induced by IFN-alpha. Copyright 2002 Wiley-Liss, Inc.
UI - 12089980
AU - Brumariu O; Miron I; Munteanu M; Enache G; Stan G; Mihailiuc C; Dimov V;
TI - Dumitrescu G; Rusu C; Mihaila D [Association between phakomatosis and neoplasia in children pathology. IV Pediatric Clinic experience]
SO - Rev Med Chir Soc Med Nat Iasi 2000 Apr-Jun;104(2):143-9
AD - Facultatea de Medicina, Universitatea de Medicina si Farmacie Gr. T. Popa, Iasi.
The risk to developing a neoplasm is increased when associated to a patient phakomatosis (Recklinghausen neurofibromatosis, Bourneville's tuberous sclerosis). We analysed 6 cases with phakomatosis and tumours, admitted in the Department of Oncopediatry, between 1993-1998; five of these children had neurofibromatosis and one Bourneville's disease. The associated tumours were hematologic malignancies (juvenile myeloid chronic leukemia) and solid tumors (rhabdomyosarcoma, hepatic carcinoma, CNS tumour, NHL optic glioma). The diagnosis was confirmed by microscopic examination of the bioptic material in all cases. Tumoral staging was performed by clinics, biology and imagistic investigations. All cases had extensive and aggressive tumours at the moment of diagnosis, We noticed a poor response and an early relapse after chemotherapy. A special follow-up and a different management has to be established for the patients with phakomatosis, in order to have a good oncological prophylaxis.
UI - 11607771
AU - Cwynarski K; Goulding R; Pocock C; Dazzi F; Craddock C; Kaeda J;
TI - Olavarria E; Kanfer E; Apperley J; Lawler M; Goldman JM Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia: association with leukaemic relapse and treatment with donor lymphocyte infusions.
SO - Bone Marrow Transplant 2001 Sep;28(6):581-6
AD - Department of Haematology, Hammersmith Hospital, ICSM, London, UK.
Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warm-type haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineage-specific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD.
UI - 12115389
AU - Atallah E; Talpaz M; O'brien S; Rios MB; Guo JQ; Arlinghaus R;
TI - Fernandes-Reese S; Kantarjian H Chronic myelogenous leukemia in T cell lymphoid blastic phase achieving durable complete cytogenetic and molecular remission with imatinib mesylate (STI571; Gleevec) therapy.
SO - Cancer 2002 Jun 1;94(11):2996-9
AD - Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
BACKGROUND: A T cell lymphoid blastic phase of chronic myelogenous leukemia (CML) is a rare occurrence, with only a few reported cases worldwide. Standard therapy for such patients is undetermined. Imatinib mesylate, a Bcr-Abl tyrosine kinase inhibitor, has shown activity in CML. METHODS: The authors report on a patient with CML and marrow as well as extramedullary nodal T cell lymphoid blastic phase who was treated with imatinib mesylate. RESULTS: The patient achieved complete morphologic and cytogenetic remission within two months of therapy. Competitive quantitative polymerase chain reaction analysis of marrow cells was negative after 15 months. Response had lasted for 26+ months at the time of writing. CONCLUSIONS: The current data suggest that imatinib mesylate may produce long-term event free survival in patients with T-cell lymphoid blastic phase CML. Its potential role alone or in combinations should be further explored in this condition. Copyright 2002 American Cancer Society.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.