Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the clinical and laboratory features of an unusual case with Sezary cell-like leukemia. Clinical manifestations were: anemia (Hb 9.4 g/dl), severe thrombocytopenia (5 x 10(9)/l), lymphocytosis (43 x 10(9)/l) and splenomegaly. There was no lymphadenopathy, hepatomegaly or skin lesions. Bone marrow trephine showed diffuse infiltration by atypical lymphoid cells. By ultrastructural analysis the cells were small to medium-size lymphocytes with nuclear features identical to Sezary cells. Immunophenotyping showed that most peripheral blood mononuclear cells were negative with B lymphoid, myeloid, and stem cell-associated markers and were also negative with most T lymphoid markers (CD2, CD4, membrane/cytoplasmic CD3, CD5 and CD8). However, they were positive with CD38 (70%), CD7 (25%) and TIA-2 (25%). Molecular analysis showed a clonal rearrangement of the TCR beta and gamma chain genes. The patient was initially treated with vincristine, doxorubicin and asparaginase and then with six cycles of CHOP, achieving a complete remission and remaining free of disease 22 months from diagnosis. Aberrant immunophenotypes are not frequent in primary T cell leukemias. This is the first case of a rare type of T cell neoplasm, Sezary cell-like leukemia, in which cells lacked most of the T cell-associated antigens.
Leukemia 1997 Aug
PMID:Sezary cell-like leukemia with atypical immunophenotype. 926 98

We report on two adult T-cell leukemia (ATL) patients whose levels of serum hyaluronic acid (HA) moved in parallel with the clinical activity of their disease. A 66-year-old man was admitted to our hospital because of unconsciousness and hypotension. Acute type ATL complicated by hypercalcemia and myelofibrosis was diagnosed. Before therapy, the level of patient's serum HA was 2,045 to 4,010 ng/ml (normal range: 50 >). After he achieved complete remission (CR) through chemotherapy, his serum HA was 36 ng/ml. Several months later, however, his ATL relapsed, and his serum HA increased to 393 ng/ml. The other patient was an 80-year-old man who had been admitted on the suspected diagnosis of ATL. Before chemotherapy, his serum HA was high (3,420 ng/ml). After CHOP therapy, he entered CR and his HA decreased to 122 ng/ml. He remains in CR with slightly elevated levels of HA (127 to 212 ng/ml), and is being followed up on an out-patient basis.
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PMID:[Adult T-cell leukemia with elevated serum hyaluronic acid levels paralleling disease activity]. 1006 97

The aim of the study was to determine the effectiveness of 2-chlorodeoxyadenosine (2-CdA) administered in 2-h i.v. infusions in the treatment of B cell chronic lymphocytic leukemia (B-CLL) in patients 55 years old and younger. One hundred and thirteen patients received three to 10 courses of 2-CdA administered at a dose of 0.12 mg/kg daily for 5 consecutive days. Sixty-seven patients were previously treated with chlorambucil and prednisone, COP and some of them also with CHOP, and 46 were untreated. Complete remission (CR) was achieved in 21 (18.6%) (19 in untreated and two in previously treated) patients and partial response (PR) in 38 (33.6%) (23 and 15, respectively) giving an overall response rate in 52.2%. The differences in CR and overall response rate between previously treated and untreated patients were statistically significant (P = 0.001). Surface immunophenotyping by flow cytometry using dual-color staining on the peripheral blood and/or bone marrow was performed in 38 patients who responded to 2-CdA therapy. Residual disease had been demonstrated in five out of 17 (29.4%) patients who were in CR and in all 21 investigated PR patients. 2-CdA-induced thrombocytopenia occurred in 24 (35.8%) of previously treated and in 13 (28.3%) previously untreated patients (P = NS). Neutropenia was observed in eight (11.9%) and in five (10.9%) patients, respectively (P = NS). Severe infections, including pneumonia and sepsis, occurred more often in previously treated (44.8%) than untreated patients (26.1%) (P < 0.05). Twenty-seven (23.9%) patients died, 11 because of infections, five because of drug-related thrombocytopenia and hemorrhage, one because of second malignancy and eight because of disease progression. In conclusion, our results indicate that 2-CdA is an effective agent in younger patients with B-CLL, especially used as a first line therapy.
Leukemia 1999 Apr
PMID:2-Chlorodeoxyadenosine (Cladribine) in the treatment of patients with chronic lymphocytic leukemia 55 years old and younger. 1021 56

We previously reported feasibility and efficacy of a monocentric pilot study of intensive sequential chemotherapy (ISC) in poor-risk aggressive non-Hodgkin's lymphoma (NHL) in patients < 60 years. To validate these results on a large cohort of patients, we designed a new and oligocentric study. After a COP (cyclophosphamide (Cy), vincristine (Vcr), prednisone (Pred) debulking, patients received four courses of high-dose CHOP (Cy, doxorubicin (Doxo), Ver, Pred), with the addition of etoposide and cisplatin during the two last courses. G-CSF was delivered after each cycle, and peripheral blood stem cells (PBSC) were used to support the two last cycles. Total duration of chemotherapy was 13 weeks, with a planned dose-intensity (DI) of 1420 mg/m2/week and 23 mg/m2/week for Cy and Doxo, respectively. Radiotherapy (involved fields) was then delivered for patients with node size > or = 5 cm at diagnosis. Forty-two patients were enrolled in this study; 36 completed the treatment and received 75% or more of the planned DI for both Cy and Doxo. Median duration of grade 4 neutropenia was 14 days (range, 2 to 28) for the regimen as a whole, and median duration of rehospitalization for febrile neutropenia was 18 days (range, 4 to 41). Overall response rate was 83%, with 29 patients (69%) in complete response (CR). Six patients failed to respond and one died of toxicity. With a median follow-up of 22.5 months (range, 10 to 42), the 3-year event-free survival (EFS) is 55% (95% CI, 39-71), while disease-free survival (DFS) is 79% (95% CI, 63-95). Ambulatory ISC is accessible and feasible in an oligocentric study. PBSC allow repeated delivery of high-dose chemotherapy cycles, and result in encouraging CR, EFS, and DFS rates for poor-risk aggressive NHL's patients.
Leukemia 1999 Jun
PMID:Intensive sequential chemotherapy (ISC 95) with growth factors and blood stem cell support in high-intermediate and high-risk (IPI 2 and IPI 3) aggressive non-Hodgkin's lymphoma: an oligocentric report on 42 patients. 1036 Mar 85

New combination therapies against hematological malignancies have recently been reported. Anti-CD20 chimeric antibody adds a therapeutic benefit to standard-dose CHOP therapy without causing significant additional toxicity in the treatment of indolent B cell lymphoma. Multidrug resistant modifiers such as PSC833 and MS209 in combination with chemotherapy are useful for treating poor risk AML patients, whose leukemia/lymphoma cells express P-glycoprotein. Fludarabine containing FL and FLAG therapy were effective in patients with AML in relapse. The early addition of chemotherapy to ATRA, and maintenance therapy with chemotherapy and intermittent ATRA, can reduce the incidence of relapse in cases of acute promyelocytic leukemia.
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PMID:[New combination therapies in hematological malignancies]. 1074 Jun 32

Natural isolates of measles virus readily infect several lymphocyte cell lines. These viruses appear to use a receptor other than CD46, the molecule to which most laboratory strains of virus bind. Methods used to identify and characterize this lymphocyte receptor for measles virus are described in this study. A binding assay with a soluble form of measles virus H protein demonstrated that B-cell lines, activated with Epstein-Barr virus, or T cells, transformed with human T-cell leukemia virus, exhibit this receptor on their cell surfaces. On the other hand, resting lymphocytes, monocytes, or immature leukocytes either failed to express or possessed reduced levels of this receptor. A cDNA library derived from B95-8 marmoset B-cell lines was used to identify this receptor through expression cloning. This molecule was shown to be CDw150, which is also known as the signaling lymphocytic activation molecule (SLAM). When the lymphocyte receptor was expressed in Chinese hamster ovary (CHOP) or human embryonic kidney (293T) cells, these cells became susceptible to lymphotropic as well as laboratory strains of measles virus. Binding assays confirmed that either lymphotropic or laboratory strains of measles virus could adhere to human or marmoset CDw150, but interaction with the mouse homolog was weak. These infections were independent of the presence of CD46 on the host cell surface. Interaction of measles virus with CDw150(SLAM) could explain the immunosuppressive properties of this virus.
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PMID:CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus. 1114 84

Chronic lymphocytic leukaemia (CLL) is a disease of late middle age and older. The majority of patients are diagnosed because of a lymphocytosis of at least 5 x 10(9)/L on an incidental blood count. It needs to be distinguished from mantle cell lymphoma and splenic marginal zone lymphoma by lymphocyte markers. The immunophenotype of CLL is sparse surface immunoglobulin, CD5+, CD19+, CD23+, CD79b-, and FMC7-. The disease is staged according to the presence of lymphadenopathy and/or splenomegaly and the features of bone marrow suppression. Most patients have an early stage of disease when diagnosed and perhaps 50% will never progress. This group of patients have a normal life expectancy and do not require treatment beyond reassurance. Progression involves an increasing white cell count, enlarging lymph nodes and spleen, anaemia and thrombocytopenia. Complications of progression include autoimmune haemolytic anaemia and thrombocytopenia, immunodeficiency, and the development of a more aggressive lymphoma. A range of prognostic factors is available to predict progression, but most haematologists rely on close observation of the patient. Intermittent chlorambucil remains the first choice treatment for the majority of patients. Combination chemotherapy offers no advantage. Intravenous fludarabine is probably more effective than chlorambucil, but no trial has yet shown a survival advantage for using it first rather than as a salvage treatment in patients not responding to chlorambucil. It is at least 40 times as expensive as chlorambucil. Cladribine may be as effective as fludarabine, although it has been used less and is even more expensive. Patients who relapse after chlorambucil should be offered retreatment with the same agent and if refractory should be switched to fludarabine, which may also be offered for retreatment on relapse. For patients refractory to both drugs, a variety of options are available. High dose corticosteroids, high dose chlorambucil, CHOP (cyclophosphamide, prednisolone, vincristine and doxorubicin), anti-CD52, anti-CD20 and a range of experimental drugs which are being evaluated in clinical trials. Younger patients should be offered the chance of treatment with curative intent, preferably in the context of a clinical trial. Autologous stem cell transplantation after achieving a remission with fludarabine has relative safety and may produce molecular complete remissions. Only time will tell whether some of these patients are cured but it seems unlikely. Standard allogeneic bone marrow transplant is probably too hazardous for most patients, but non-myeloablative regimens hold out the hope of invoking a graft-versus-leukaemia effect without a high tumour-related mortality. Trials of immunotherapy are exciting options for a few patients in specialised centres.
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PMID:Achieving optimal outcomes in chronic lymphocytic leukaemia. 1136 85

Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period. Median age was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70 Gy) before 1980 and combination chemotherapy after 1980. Six patients were treated with first-line radiotherapy and they achieved complete remission (CR). Two subsequently received combination chemotherapy. Five of those patients remained in complete remission, after 97+ to 277+ months. Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases, and COP in five cases. Only three of them achieved CR, five had partial response and four had progressive disease. Five of the seven patients treated with CHOP did not achieve complete remission. The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR. Finally, two patients were treated with alternated chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+ months. Median survival was not reached in patients who received front-line radiotherapy, and was 35 months in patients who received front-line chemotherapy. These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to give favorable results, whereas its results are poorer when administered after resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy, or alternated chemotherapy-radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospectively in this type of NHL.
Leukemia 2001 Jul
PMID:Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx. 1145 83

Anthracyclines have been in clinical practice since the 1960s and represent one of the most commonly used classes of anticancer drugs. Doxorubicin (adriamycin) is one of the first anthracyclines in clinical use, has a broad anti-tumor spectrum, and has been used against hematopoietic malignancies such as lymphoma, myeloma and leukemia, and solid tumors such as breast cancer, ovarian cancer and sarcomas. There are two chemotherapeutic regimens containing doxorubicin that have been established as the state of the art therapy against malignant lymphomas. One is ABVD therapy for Hodgkin's lymphoma, and the other is CHOP therapy for aggressive non-Hodgkin's lymphoma (NHL). In these regimens as well as the regimen for breast cancer, doxorubicin is delivered by bolus intravenous infusion for 30 minutes to one hour. The use of continuous infusion schedules of doxorubicin for 72 to 96 hours has been reported to reduce the incidence of cardiac toxicity somewhat, providing a pharmacokinetic basis for the hypothesis that high peak concentrations are associated with an increased incidence of cardiotoxicity. VAD regimen for myeloma, and EPOCH regimen for relapsed aggressive NHL have been reported and used. However, this approach is not widespread because of concern over compromising antitumor efficacy, unpredictable toxicities, and logistical issues. Continuous infusion schedules of doxorubicin might be reevaluated for the clinical benefit especially for patients with breast cancer treated by trastuzumab and doxorubicin, because trastuzumab was reported to enhance cardiac toxicity.
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PMID:[Adriamycin (doxorubicin)]. 1168 Dec 38

The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P <0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI > or =2 had 8 months median OS as compared to 36 months median OS for patients with IPI <2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5+ NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients.
Leukemia 2001 Nov
PMID:Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype. 1220 Jul 19


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