1/12. Imatinib mesylate in philadelphia chromosome-positive leukemia of childhood.BACKGROUND: Initial treatment for adult patients with philadelphia chromosome-positive (Ph[ ]) chronic myelogenous leukemia (CML) now includes imatinib mesylate. However, to our knowledge, there are few data regarding imatinib safety, efficacy, and response monitoring in patients age < 18 years. methods: In the current series, the authors report 5 consecutive patients ages 20 months to 12 years with Ph leukemia who were treated with imatinib and evaluated for a response using cytogenetics, fluorescent in situ hybridization (FISH), and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on serial bone marrow aspirations. Doses of imatinib were escalated as tolerated from a starting dose of 400 mg/m2 (patients with a body surface area [BSA] < 1 m2) or 400 mg/day (patients with a BSA > 1 m2). RESULTS: After the initiation of imatinib therapy, all 4 patients with CML were found to have no detectable Ph chromosome by cytogenetics (median of 198 days of imatinib therapy; range, 138-346 days), FISH (median of 285 days of imatinib therapy; range, 138-366 days), and real-time RT-PCR (median of 287 days of imatinib therapy; range, 224-366 days). One patient with Ph acute mixed lineage leukemia achieved a morphologic disease remission with standard chemotherapy, but within 10 months had increasing Ph positivity in consecutive bone marrow aspirations. Imatinib was added to the intensive leukemia therapy, and within 26 days there were no detectable Ph cells in the bone marrow. Mild thrombocytopenia was noted in two patients and transient mild hepatic toxicity was noted in one patient. CONCLUSIONS: Imatinib mesylate was found to be effective in inducing undetectable residual disease in a small cohort of pediatric patients with Ph leukemia. Further studies of the use of imatinib in childhood Ph malignancies are needed.- - - - - - - - - - ranking = 1keywords = residual disease, residual (Clic here for more details about this article) |
2/12. association of cytogenetic abnormalities with detection of BCR-ABL fusion transcripts in children with T-lineage lymphoproliferative diseases (T-ALL and T-NHL).Detection of philadelphia chromosome (Ph) in childhood T-lineage acute lymphoproliferative disorders is a rare event. Additional cytogenetic abnormalities are particularly uncommon in ALL. We here report two cases with T lineage acute lymphoproliferative disorders (T-ALL and T-NHL) presenting with both cytogenetic alterations and BCR-ABL fusion transcripts, associated with an aggressive presentation and a poor outcome. We point out firstly on the cytogenetic aberrations, supporting the hypothesis of multi-lineage involvement of ALL expressing Ph chromosome; secondly, on the persistence of T-cell leukemic clone detected by minimal residual disease (MRD) analysis, despite of the early disappearance of BCR-ABL fusion transcript.- - - - - - - - - - ranking = 18.591609821573keywords = minimal residual disease, minimal residual, residual disease, residual (Clic here for more details about this article) |
3/12. Blastic mantle cell lymphoma developing concurrently in a patient with chronic myelogenous leukemia and a review of the literature.Non-Hodgkin's lymphoma (NHL) occurring as a synchronous malignancy with chronic myelogenous leukemia (CML) is rare. To our knowledge, this is the first case reported of a patient who developed mantle cell lymphoma (MCL) after therapy with imatinib mesylate for CML. After a 3-year history of CML, the patient developed a lymphocytosis associated with diarrhea, anorexia, and weight loss. Imaging studies revealed abdominal adenopathy and extensive lymphomatous infiltration of the liver, stomach, pancreas, and kidneys. Flow cytometric and cytogenetic studies were consistent with MCL. fluorescence in situ hybridization (FISH) of the bone marrow revealed a genetically distinct lymphoid neoplasm rather than an extramedullary blast crisis of CML. The development of lung cancer, prostate cancer, CML and MCL in this patient suggests a genetic predisposition, although other factors, including environmental exposures and therapy with imatinib mesylate could have had a contributory or synergistic role in the development of MCL.- - - - - - - - - - ranking = 0.00010356781280326keywords = cancer (Clic here for more details about this article) |
4/12. Existence of leukemic clones resistant to both imatinib mesylate and rituximab before drug therapies in a patient with philadelphia chromosome-positive acute lymphocytic leukemia.Imatinib mesylate and rituximab are molecularly targeted drugs against the BCR-ABL fusion protein and the CD20 antigen, respectively. Although these drugs have excellent anticancer effects, a major concern is drug resistance. We have investigated the case of a patient with philadelphia chromosome-positive and CD20 acute lymphocytic leukemia who acquired resistance to imatinib and rituximab. Imatinib therapy resulted in prompt cytogenetic remission, but resistance developed shortly thereafter. Sequencing of the kinase domain of the ABL gene and allele-specific polymerase chain reaction analysis revealed a point mutation resulting in an E255V substitution that was present before the therapy. After the patient received mild chemotherapy followed by rituximab administration, hematologic and cytogenetic remission was sustained for 5.5 months. The recurrent leukemic cells after the rituximab therapy showed not only the E255V mutation in the ABL gene but also loss of the CD20 antigen due to impaired transcription of the CD20 gene. The results of 2-color flow cytometry analysis showed that a small population of CD20(-) leukemic cells existed before the imatinib therapy. These results suggest that leukemic subclones carrying a genetic perturbation of the targeted molecules for both imatinib and rituximab were present before the therapies. The preexistence of primary resistant clones suggests the inability of combination therapy with 2 molecularly targeted drugs to overcome drug resistance in leukemia.- - - - - - - - - - ranking = 5.1783906401629E-5keywords = cancer (Clic here for more details about this article) |
5/12. Detection of trisomy 8 in donor-derived Ph- cells in a patient with Ph chronic myeloid leukemia successfully treated with Imatinib (STI571) in relapse after allogeneic transplantation.Recent data suggest that STI571 (Imatinib) induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT). However, little is known about molecular responses to STI571 and the duration of leukemia-free survival in these patients. We report on a 43 year old female patient who presented with a relapse from Ph CML in December 2000. Five years earlier she had received an SCT from an unrelated male donor in accelerated phase. At the time of relapse, she presented with marked leukocytosis (89,000 microl) and 10% blasts. In December 2000, therapy with Imatinib was started. After 3 months, the karyotype showed an XY, with trisomy 8 in about 50% of all metaphases, but without evidence of residual Ph cells. Moreover, in response to Imatinib, BCR/ABL transcripts decreased and were no longer detectable after 6 months. After a total observation period of 36 months, the patient is still in complete cytogenetic and molecular remission without signs of occurrence of a donor-type hematopoietic neoplasm or CML relapse. These data suggest that Imatinib is a useful agent for long term treatment of relapsed CML after allogeneic SCT.- - - - - - - - - - ranking = 0.005400343346452keywords = residual (Clic here for more details about this article) |
6/12. A case of basophilic leukemia bearing simultaneous translocations t(8;21) and t(9;22).We report a case of basophilic leukemia with simultaneous translocations of t(8;21) and t(9;22). The patient's clinical and hematologic findings were characteristic only of t(9;22) but not of t(8;21). This unusual cytogenetic phenomenon raises a challenge to the current concepts of primary chromosomal abnormalities in cancer.- - - - - - - - - - ranking = 5.1783906401629E-5keywords = cancer (Clic here for more details about this article) |
7/12. Philadelphia-chromosome-negative chronic myelogenous leukemia with incomplete trisomy 1q following chemotherapy for ovarian carcinoma.A 59-year-old woman was treated with surgery followed by monthly injections of the alkylating agent thiotepa for a granulosa cell tumor of the left ovary. Chemotherapy was continued for 22 years. At the age of 84, chronic myelogenous leukemia (CML) developed. Cytogenetic studies revealed incomplete trisomy of the long arm of chromosome No. 1 as the only karyotypic abnormality. No Philadelphia chromosome was detected. The significance of trisomy 1q as an isolated cytogenetic abnormality in CML and the occurrence of CML following treatment of ovarian cancer are discussed.- - - - - - - - - - ranking = 5.1783906401629E-5keywords = cancer (Clic here for more details about this article) |
8/12. Infusion of tumor-contaminated bone marrow for autologous rescue after high-dose therapy leading to long-term remission in a patient with relapsed philadelphia chromosome-positive acute lymphoblastic leukemia.We report a female patient with relapsed philadelphia chromosome-positive acute lymphoblastic leukemia remaining in long-term second remission after high-dose radiochemotherapy followed by autologous stem cell rescue with bone marrow showing evidence of residual disease. The philadelphia chromosome and a positive signal for the BCR/ABL p185 translocation by the polymerase chain reaction were detected in the harvested marrow. After mafosfamide-purged marrow failed to engraft, her unpurged 'back-up' bone marrow was also infused. Control marrow examinations after recovery were repeatedly positive for the BCR/ABL translocation on PCR analysis turning negative 30 months after high-dose therapy. She remains in unsustained complete clinical remission for 48 months showing no evidence of leukemia by cytological and cytogenetic analyses.- - - - - - - - - - ranking = 1keywords = residual disease, residual (Clic here for more details about this article) |
9/12. Case report of spontaneous remission of cytogenetic relapse of chronic myelogenous leukemia suggestive of progression to blast crisis after allogeneic bone marrow transplantation.Detection of the chronic myelogenous leukemia (CML)-related marker, the bcr/abl m-rna transcript, in blood or bone marrow of patients with CML in hematologic remission after allogeneic bone marrow transplantation (allo-BMT) may be associated with the presence of minimal residual disease but does not uniformly predict hematologic relapse. In contrast, when there is cytogenetic reappearance of the Philadelphia (Ph1) translocation [t(9;22)(q34;q11)] along with additional cytogenetic abnormalities, especially more than 2 years after BMT, progression to hematologic relapse and acceleration of CML usually occur. An exception to this rule may be our patient, who was a 29-year old white woman diagnosed with Ph1-positive CML by cytogenetics. She was initially treated with hydroxyurea. An allo-BMT was performed 4 months after the diagnosis, while the patient was still in the first chronic phase of her disease, her HLA-identical brother serving as bone marrow (BM) donor. The conditioning regimen for BMT consisted of cytosine arabinoside, cyclophosphamide, total body irradiation, splenic irradiation, and intrathecal methotrexate. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A and methotrexate. Her hospital course was unremarkable and without evidence of acute GVHD. Six months after transplantation, the patient had mild chronic GVHD and was treated with azathioprine and prednisone for 6 months. A year later, she recurred with mild chronic GVHD. She was treated with azathioprine alone for 5 months. Subsequently, she received cyclosporin A and prednisone for 8 months, with resolution of her symptoms. Serial BM cytogenetic studies showed normal male donor karyotypes 12 and 24 months after BMT. At 36, 42, and 50 months after BMT, reappearance of the Ph1 was noted along with some cells with additional cytogenetic abnormalities, including t(6;14)(p21;q32). The breakpoint involvement of 14q32, the heavy chain Ig locus, in the new clone may be indicative of B-lymphoid lineage-based evolution. The abnormal clones disappeared 56 months from BMT and remained absent through 69 months after BMT. The patient has remained in hematologic remission during her entire post-BMT course. Clinically, she continues to do well without immunosuppressants at presently 69 months after BMT. The reappearance of the Ph1 chromosome could be associated with the immunosuppressive therapy given for chronic GVHD. This case supports the concept that immunologic mechanisms may be important in the eradication of CML after allo-BMT, and even cytogenetic evidence of blast crisis CML may spontaneously remit after allo-BMT.- - - - - - - - - - ranking = 18.591609821573keywords = minimal residual disease, minimal residual, residual disease, residual (Clic here for more details about this article) |
10/12. Disappearance of Ph1 chromosome with intensive chemotherapy and detection of minimal residual disease by polymerase chain reaction in a patient with blast crisis of chronic myelogenous leukemia.We diagnosed a patient with chronic myelogenous leukemia (CML) in chronic phase (CP) on the basis of clinical findings, Ph1 chromosome detected by cytogenetic analysis, and bcr-abl fusion mRNA detected by reverse transcriptase-dependent polymerase chain reaction (RT-PCR). One month after diagnosis, the patient developed extramedullary blast crisis in the lymph nodes, and then medullary blast crisis in the bone marrow, in which different surface markers were shown. Combination chemotherapy with BH-AC, VP16, and mitoxantrone was administered; this resulted in rapid disappearance of the lymphadenopathy, restoration of normal hematopoiesis, and no Ph1 chromosome being detected by cytogenetic analysis. RT-PCR performed to detect the residual Ph1 clone revealed that although the Ph1 clone was preferentially suppressed, it was still residual. The intensive chemotherapy regimen preferentially suppressed the Ph1-positive clone and led to both clinical and cytogenetic remission in this patient with BC of CML; we suggest that RT-PCR is a sensitive and useful method for detecting minimal residual disease during the clinical course of this disease.- - - - - - - - - - ranking = 92.968849794556keywords = minimal residual disease, minimal residual, residual disease, residual (Clic here for more details about this article) |
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