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A Tefferi

Publications and source records attributed to A Tefferi.

At least 181 records · Page 10Linked to original sources
PubMed1994

Issues in the diagnosis and management of essential thrombocythemia.

OBJECTIVE: To summarize the current trends in the diagnosis and management of essential thrombocythemia (ET) and to discuss the treatment of young and pregnant patients with ET. DESIGN: We review our experiences in the diagnosis and management of ET. MATERIAL AND METHODS: A definitive diagnosis of ET at initial examination is seldom possible because of the low incidences of associated clonal cytogenetic abnormalities and palpable splenomegaly. The criteria of the Polycythemia Vera Study Group for the diagnosis of ET are provided, as are the clinical and laboratory features that help to distinguish ET from reactive thrombocytosis. RESULTS: Patients with ET have an almost normal life expectancy if thrombohemorrhagic complications are controlled. Although a previous history of thrombosis is an established risk factor for further episodes, the adverse effects of extreme thrombocytosis and age are less well defined. Determining which patients require therapy is controversial. The management of young or pregnant patients necessitates special considerations. CONCLUSION: Until additional data become available, no strong recommendations can be given in support of or against specific therapy for asymptomatic young patients. We favor treatment in asymptomatic patients with cardiovascular risk factors but not in asymptomatic women who are pregnant or are of childbearing age.

Female↗
PubMed1994

Acute lymphocytic leukemia in adults: a retrospective study and analysis of current management options.

OBJECTIVE: To examine current therapeutic modalities for acute lymphocytic leukemia (ALL) in adults, analyze prognostic variables, and offer treatment recommendations. DESIGN: We reviewed our experience with 90 adult patients with ALL examined at the Mayo Clinic between 1982 and 1992 and used it as a background for discussion of prognostic factors and management options in adult patients with ALL. MATERIAL AND METHODS: The pretreatment characteristics of patients, types of induction chemotherapy, and postremission treatment, including bone marrow transplantation (BMT), were analyzed for prognostic significance for each of three outcomes: complete remission (CR) rate, duration of CR, and overall survival of patients. RESULTS: Of the 90 study patients, 80 had received induction chemotherapy. Overall long-term survival for treated patients was 25%. None of the 10 patients younger than 18 years of age underwent BMT, and their long-term survival was 80%. Of the other 70 patients, who were 18 years old or older, 42 (60%) had a CR with induction chemotherapy. Of these 42 patients, 31 did not undergo BMT, and their long-term survival was less than 13%. BMT was done in six patients during a first CR (with 100% survival), in four during a later CR (with 50% survival), and in six with disease (with 17% survival). The median age of patients who received chemotherapy was 50 years (range, 19 to 87) and that of patients who underwent BMT was 34 years (range, 18 to 46). Overall, age was the only significant prognostic factor. CONCLUSION: With our application of current chemotherapy, the outcome in adult patients (18 years old or older) with ALL was dismal. The results were considerably better in patients younger than 18 years of age or in those who underwent BMT as post-remission therapy. Comprehensive assessment of our experience and that in the literature, however, did not resolve issues about current management. Participation of patients in comparative trials is critical for determining the best therapy for ALL in adults.

Adolescent↗
PubMed1994

Acute porphyrias: diagnosis and management.

To summarize recent information about acute porphyrias and to provide clinicians with a practical diagnostic and management approach, we reviewed the pertinent literature and our clinical experience. The acute porphyrias are characterized by recurrent attacks of abdominal pain with or without additional manifestations of autonomic dysfunction or neuropsychiatric symptoms. On the basis of the potential of these disorders to affect the skin, they are further subdivided into neuroporphyrias and neurocutaneous porphyrias. During acute attacks, acute porphyria is always associated with increased levels of urinary porphyrin precursors. Between attacks, patients with neurocutaneous porphyrias may have normal urinary porphyrins; therefore, stool porphyrins, which are invariably increased, are the most helpful. Latent disease can be detected by the measurement of either urinary and stool porphyrins or cellular enzyme activity. Specific intravenous therapy with hematin has resulted in biochemical remissions, but its clinical benefit remains controversial. Measurement of urinary and stool porphyrins or porphyrin precursors is critical for the diagnosis of clinically overt acute porphyria. Enzyme assays are helpful in supporting the diagnosis but are best used to identify family members with latent disease. Preventive measures and supportive therapy are the mainstays of current management of patients with porphyria.

Acute Disease↗
PubMed1994

Measurement of the intensity of cell surface antigen expression in B-cell chronic lymphocytic leukemia.

Immunophenotyping of peripheral blood lymphocytes from 95 patients with B-cell chronic lymphocytic leukemia (B-CLL) was performed to estimate surface membrane intensity of the HLA-DR, CD20, and light-chain antigens. Cases were classified as having weak, moderate, or strong intensity by a standard slide immunocytochemical method, and the fluorescence intensity (FI) was measured by flow cytometry in molecules of equivalent soluble fluorescence (MESF). Staining intensity was strongest for HLA-DR; with both methods, 94 cases were classified as strong. For CD20, 67% were weak, 27% moderate, and 6% strong; the mean MESF values were 31.7, 66.4, and 177.4 x 10(3), respectively (P < .001). Thirty-nine percent had weak surface light-chain staining, 50% moderate, and 11% strong; the mean MESF values were 4.9, 7.5, and 16 x 10(3), respectively (P = .005). These results indicate that the FI of cell surface antigens can be estimated and quantified by flow cytometry. Because of the wide overlap of FI values among the three groups, an exact correlation was not found between the two methods of classifying intensity of surface antigen expression. The usefulness of these quantitative measurements needs further analysis in clinical trials.

Antigens, CD↗
PubMed1994

Phase I study of combined 2-chlorodeoxyadenosine and chlorambucil in chronic lymphoid leukemia and low-grade lymphoma.

PURPOSE: We conducted a dose-escalation study of 2-chlorodeoxyadenosine (2-CdA) added to a standard fixed dose of chlorambucil to evaluate the toxicity of the combined regimen in patients with chronic lymphocytic leukemia (CLL) and low-grade lymphoma. PATIENTS AND METHODS: A total of 15 adults with relapsed or refractory CLL or low-grade lymphoma were to receive chlorambucil orally (30 mg/m2) every 2 weeks. Also, groups of three patients were to receive escalating doses of continuous intravenously administered 2-CdA at 1, 2, or 4 mg/m2/d for 7 days repeated at monthly intervals. All patients had pharmacokinetic studies during the first cycle of 2-CdA therapy; the results were compared with other institutional phase I studies in which comparable amounts of 2-CdA were administered by bolus infusion for 5 days. RESULTS: The maximal-tolerated dose of 2-CdA that could be combined with chlorambucil was 2 mg/m2/d for 7 days for a maximum of two courses. At a higher dose level of 2-CdA or at the maximal-tolerated dose level given for more than two courses, severe and protracted pancytopenia, sometimes associated with life-threatening infections, was noted. Nonhematologic toxicities were limited to moderate degrees of nausea, vomiting, anorexia, and fatigue. Results of the pharmacologic studies suggested that 2-CdA clearance was independent of administration schedule and was unaffected by concomitant administration of chlorambucil. CONCLUSION: These observations suggest the possibility of combining two cycles of continuous intravenously administered 2-CdA (2 mg/m2/d for 7 days) with standard doses of oral chlorambucil to test the efficacy of the combination regimen in phase II trials.

2-Chloroadenosine↗
PubMed1994

Treatment of refractory T-cell chronic lymphocytic leukemia with purine nucleoside analogues.

This report describes two cases of T-cell chronic lymphocytic leukemia (T-CLL) treated with purine nucleoside analogues. One patient had CD8+, CD3+ large granular lymphocytosis (LGL) producing transfusion-dependent anemia and was refractory to chemotherapy. Treatment with four cycles of fludarabine produced a clinical complete remission and a molecular genetic partial remission that has been durable for > 15 months. The other patient had CD4+ T-prolymphocytic leukemia and was unresponsive to both fludarabine and 2-chlorodeoxyadenosine. Further trials of these agents are warranted in T-CLL, especially the LGL variant.

2-Chloroadenosine↗
PubMed1994

The 5q- syndrome: a scientific and clinical update.

The 5q- syndrome is a subset of the myelodysplastic syndromes characterized by hypolobulated micromegakaryocytic hyperplasia and an interstitial deletion of the long arm of chromosome 5. In this concise review, we discuss the current understanding in regard to the genetic basis of the disorder and provide an updated clinical report on 43 patients with the disease who were seen at our institution.

Chromosome Deletion↗
PubMed1994

Detection of trisomy 12 by FISH in untreated B-chronic lymphocytic leukemia: correlation with stage and CD20 antigen expression intensity.

We studied cells from 30 controls and 85 cases of untreated B-chronic lymphocytic leukemia (CLL) with a fluorescence in-situ hybridization (FISH) technique utilizing a probe to chromosome 12. By use of a threshold of > 2% for trisomy 12 for the CLL cases (the mean +3 SD for controls was 1.3%), 20% (17/85) were trisomy 12. The mean % cells positive was 32.6 (median, 39.4; range, 2.4-79.1). There was a trend toward an higher incidence of trisomy 12 in patients with Rai stages 1-4 vs Rai 0 (p = 0.16). Forty-seven % (8/17) of patients with trisomy 12 had strong intensity CD20 antigen expression compared to 21% (14/68) of patients without trisomy 12 (p = 0.03). Trisomy 12 associated with CLL is easily detected by FISH with an overall incidence of 20%. This technique should be applied to larger groups of patients to confirm the potential variation among Rai stages and immunophenotypic subgroups.

Antigens, CD↗
PubMed1993

The 5q- syndrome: a single-institution study of 43 consecutive patients.

A favorable prognosis and a low rate of leukemic transformation has been attributed to the 5q- syndrome, a myelodysplastic syndrome (MDS) characterized by macrocytic anemia, hypolobulated micromegakaryocytic hyperplasia, and an interstitial deletion of chromosome 5. We examined the characteristics and outcome of 43 consecutive patients in our institution strictly defined by morphologic criteria and a solitary 5q- cytogenetic defect. The median age at diagnosis was 68 years, with a clear female predominance (7:3). Eighty percent of the patients were red blood cell transfusion-dependent at diagnosis and all untransfused patients had macrocytic indexes. In contrast, significant neutropenia or thrombocytopenia was rare. The French-American-British (FAB) class distributions were RA (72%), RARS (7%), RAEB (16%), and RAEB-IT (5%). At a median follow-up of 31 months, 56% of the patients survive, with a projected median survival of 63 months. The incidence of acute leukemia was 16% and was uniformly fatal. Clinical hemosiderosis occurred in 28% of the patients, resulting in two deaths. Neither survival nor the risk of leukemic transformation was predictable from initial clinical parameters, including FAB classification, Bournemouth score, and degree of aneuploidy. The lack of significant neutropenia and thrombocytopenia seemed to account for a very low incidence of infection and bleeding resulting in a prognosis equal or superior to historical patients with MDS. Therapeutic endeavors, including the use of corticosteroids, androgens, cis-retinoic acid, pyridoxine, and danazol, were largely unsuccessful.

Acute Disease↗
PubMed1993

Karyotypic analysis in primary myelodysplastic syndromes.

Cytogenetics has provided new insights into the biology and pathogenesis of myelodysplastic syndromes. In patients with refractory anemia, it has provided proof of clonality and has helped differentiate chronic myelomonocytic leukemia from chronic myeloid leukemia. As a prognostic tool, cytogenetics has been predictive of duration of survival and leukemic transformation. However, its role as an independent prognostic factor compared with recent prognostic scoring systems remains to be determined. New techniques such as fluorescent in situ hybridization using chromosome-specific DNA probes may expand the usefulness of cytogenetics. The prognostic impact of cytogenetics may not be fully realized until more effective treatments become available.

Adult↗
PubMed1993

Prognostic features and survival in young adults with early/intermediate chronic lymphocytic leukemia (B-CLL): a single institution study.

Information regarding natural history and prognostic factors for early/intermediate B-cell chronic lymphocytic leukemia (B-CLL) in young adults is limited. We analysed 62 young adults (< or = 50 years old) with early/intermediate B-CLL who were seen at our institution during initial diagnosis over a 15-year period. These patients had been followed for a median duration of 7 years. Median age for the entire group was 44 years and 72% were > or = 40 years old. Actuarial median survival from initial diagnosis for the entire group was 140 months. Upon univariate analysis, significant survival advantage was observed in patients with Rai stages 0 and 1 versus stage II disease (median survival 140 versus 60 months, p = 0.01) and in those with lymphocyte doubling time (LDT) of > 1 year versus < or = 1 year (median survival 150+ versus 94 months, p = 0.06). Similarly there was a trend towards longer survival in patients with a leucocyte count of < or = 50,000/microliters when compared to those with higher counts although the difference was not statistically significant. The bone marrow infiltration pattern was not prognostically useful. Upon multivariate analysis, only Rai stage and LDT were prognostically useful. Patients who did not respond to initial therapy with alkylating agents had the worst prognosis, with a median survival of only 19 months. Assessment of presenting clinical stage, LDT, and degree of initial treatment response may prompt earlier consideration of alternative therapeutic modalities such as purine nucleoside analogs or bone marrow transplantation in younger patients with early/intermediate B-CLL.

Adolescent↗
PubMed1992

Secondary T-cell lymphoma in the setting of nodular lymphocyte predominance Hodgkin's disease.

Lymphocyte predominance Hodgkin's disease (LPHD) can be histologically subdivided into a nodular and diffuse variety. The two subtypes differ in immunophenotypic characteristics but have a similar long-term clinical outcome. Nodular LPHD has immunophenotypic and histological characteristics suggestive of a B-cell derived neoplastic process. Nodular LPHD is associated with an increased risk of secondary large cell lymphoma (LCL). Gene rearrangement studies in some of these cases have revealed a B-cell clonal process, further supporting the association between nodular LPHD and the B-cell system. In addition, it has been suggested that the apparent secondary LCL, at least in some cases, may represent a histologic progression of nodular LPHD. We report a unique case of T-cell lymphoma, confirmed by T-cell receptor gene rearrangement studies, which developed in the setting of nodular LPHD. Our observation demonstrates that the association of nodular LPHD and LCL is complex and that LCL developing in the context of nodular LPHD may be an independent secondary process sometimes involving T-cell lymphomas.

Adult↗
PubMed1992

Splenectomy in advanced chronic lymphocytic leukemia: a single institution experience with 50 patients.

PURPOSE: To assess the efficacy of splenectomy in the treatment of refractory cytopenias associated with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: The histories of 57 patients with CLL who underwent splenectomy at the Mayo Clinic between 1975 and 1991 were retrospectively reviewed. Of the 57 patients, 50 underwent splenectomy for reasons directly related to their disease process such as cytopenias or symptomatic splenomegaly. The histories from these 50 patients were studied to assess the response to splenectomy and the operative morbidity and mortality. RESULTS: Ninety-four percent of patients were in Rai stage III or IV with extensive marrow infiltration, massive splenomegaly, and cytopenias refractory to chemotherapy. A positive response to splenectomy was defined at 3 months of follow-up as: (1) a hemoglobin level of 11 g/dL or greater in a patient with a preoperative value less than 11 g/dL; or (2) a platelet count of 100 x 10(3)/mm3 or greater in a patient with a preoperative value less than 100 x 10(3)/mm3. A positive response was achieved in 77% of patients with anemia, 70% of patients with thrombocytopenia, and 64% of patients with both anemia and thrombocytopenia. The response was sustained at 1 year of follow-up in 86%, 84%, and 85% of the patients, respectively. Postoperative transfusion requirements decreased correspondingly. The operative morbidity was 26%, and the operative mortality was 4%. The mean duration of hospitalization was 9.8 days (median: 9 days; range: 5 to 24 days). The actuarial median survival after splenectomy was 41 months in responders and 14 months in nonresponders. We found no preoperative parameters that were clearly predictive of a poor hematologic response. In particular, outcome was not affected by preoperative spleen size or the degree of marrow infiltration by CLL. All patients with symptomatic splenomegaly had an improved sense of well-being. CONCLUSION: In this, the largest single institution study to date, we found splenectomy to be efficacious in providing durable remissions of refractory cytopenias and in relieving symptomatic splenomegaly in the majority of patients with CLL. The procedure is associated with a low perioperative mortality. Although the impact on survival is uncertain, the improved peripheral blood counts may allow the administration of adequate doses of myelosuppressive chemotherapy.

Actuarial Analysis↗