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A Tefferi

Publications and source records attributed to A Tefferi.

At least 199 records · Page 11Linked to original sources
PubMed1992

Pyoderma gangrenosum-like ulcer in a patient with large granular lymphocytic leukemia.

Large granular lymphocytic leukemia refers to a clonal expansion of lymphocytes that have abundant cytoplasm and azurophilic granules. The disease is characterized clinically by chronic neutropenia and it may be associated with recurrent pyogenic infections. Except for these infections, cutaneous manifestations of this disease have not been well characterized. We describe a patient with large granular lymphocytic leukemia, which was confirmed by molecular genetics studies, who had a pyoderma gangrenosum-like ulcer on his leg. Results of an evaluation of the histologic characteristics and the leukocytic immunophenotype of a skin biopsy specimen from the ulcer demonstrated large granular lymphocytes within the blood vessels. Cutaneous ulceration may be a manifestation of large granular lymphocytic leukemia, and this disease should be considered when diagnosing patients with otherwise unexplained pyoderma gangrenosum-like ulcers of the skin.

Complement C3↗
PubMed1992

A clinical update on chronic lymphocytic leukemia. II. Critical analysis of current chemotherapeutic modalities.

Not all patients with B-cell chronic lymphocytic leukemia require therapy. Patients with stable early stage disease do not need treatment, whereas those with progressive early stage disease or advanced stage disease do. The standard initial therapeutic regimen is orally administered chlorambucil and prednisone. The overall response rate to initial chemotherapy is approximately 80%; the median duration of response is 2 years. Conventional chemotherapy, however, does not provide long-term remission for patients in whom the disease becomes refractory to chlorambucil. For such patients, alternative treatment approaches including the use of purine nucleoside analogues or bone marrow transplantation may be considered. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are three analogues of the naturally occurring deoxypurine nucleoside, deoxyadenosine, and all have shown activity in chronic lymphocytic leukemia. Overall response rates of 57 to 79% have been reported with use of fludarabine. A dose-related toxic effect is myelosuppression. Experience with bone marrow transplantation is limited. The number of eligible patients with histocompatible sibling donors is low. The future role of allogeneic bone marrow transplantation in patients with B-cell chronic lymphocytic leukemia will depend on the ability to identify poor-risk groups and the long-term therapeutic efficacy of the purine nucleoside analogues or other new agents.

2-Chloroadenosine↗
PubMed1992

Outcome of recipients of bone marrow transplants who require intensive-care unit support.

To determine the outcome and prognostic factors associated with bone marrow transplantation (BMT), we reviewed the clinical course of 35 adult recipients of such a transplant who were admitted to our intensive-care unit (ICU). This constituted 24% of patients who underwent BMT for treatment of hematologic disorders during the study period. The reasons for admission to the ICU were postsurgical care in 5, respiratory failure in 25, shock in 4, and renal failure in 1. The in-hospital mortality was 20% for the postsurgical patients and 87% for the others. None of the postsurgical patients required mechanical ventilation, whereas 90% of the others did, and the associated mortality was 93%. Infection was the cause of the respiratory failure in all but 3 of the 25 patients and was associated with 95% mortality. Complications that involved multiple organs increased the mortality to 100%. No significant differences were found in age, sex, type of BMT, serologic tests for cytomegalovirus, history of graft-versus-host disease, conditioning regimen for BMT, and duration of stay in the ICU and the hospital between survivors and nonsurvivors. The APACHE II (acute physiology and chronic health evaluation) prognostic scoring system underestimated mortality and had no correlation with the duration of stay in the ICU or the hospital. Vasopressors, total parenteral nutrition, and transfusion of blood components in the ICU had no influence on the outcome. Open-lung biopsy was helpful in making specific diagnoses, and pulmonary artery catheters were used in most patients to guide therapy but did not improve survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers↗
PubMed1992

Cytogenetic and molecular detection of residual leukemic cells after allogeneic bone marrow transplantation in chronic granulocytic leukemia.

Allogeneic bone marrow transplantation (BMT) is a therapeutic modality with a curative potential for chronic granulocytic leukemia. Approximately 20% of patients have a hematologic relapse after BMT. The frequency of cytogenetic or molecular relapse (or both), despite hematologic remission, is reportedly higher. We performed allogeneic BMT in 32 patients with chronic granulocytic leukemia by using unmanipulated donor marrow and a conditioning regimen that consisted of cyclophosphamide and total-body irradiation. Of these 32 patients, 23 had cytogenetic studies after BMT. Seven of these patients had cytogenetically detectable Philadelphia chromosomes some time after BMT, during hematologic remission. The Philadelphia chromosome was detected transiently in two patients, and the fraction of abnormal metaphases exceeded 25% in three patients. None of the patients with negative results of cytogenetic studies or with the presence of the Philadelphia chromosome in less than 25% of analyzed metaphases had a clinical relapse, whereas two of the three patients with more than 25% abnormal metaphases had clinical relapses. Our results suggest that the detection of more than 25% abnormal metaphases during cytogenetic studies for chronic granulocytic leukemia after BMT may imply an incipient clinical relapse. We review the current literature that discusses isolated cytogenetic or molecular relapses of chronic granulocytic leukemia after BMT.

Academic Medical Centers↗
PubMed1992

A clinical update on chronic lymphocytic leukemia. I. Diagnosis and prognosis.

B-cell chronic lymphocytic leukemia (B-CLL) is a relatively indolent hematologic malignant disease that, despite a good response to nonaggressive orally administered chemotherapy, currently remains incurable. The overall median duration of survival is more than 5 years, and the presence of anemia or thrombocytopenia adversely affects prognosis. B-CLL is readily diagnosed because of the characteristic and specific phenotypic expressions of the neoplastic cells. Clinical staging continues to be the best prognostic indicator in B-CLL. In addition, cytogenetic status, pattern of leukemic infiltration in the bone marrow, and lymphocyte doubling time are now considered to have additional prognostic value. In this article, the diagnostic evaluation of lymphocytosis is discussed, and an updated analysis on the prognostic determinants of B-CLL is provided. The second part of this clinical update, which reviews current chemotherapeutic modalities, will be published in the subsequent issue of this journal.

Bone Marrow↗
PubMed1992

Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide.

The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characteristics of either cytotoxic T lymphocytes (CD3+,CD8+) or natural killer (NK) cells (CD3-,CD15+). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked DNA analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked DNA analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated magnetic beads. The DNA of these cells was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy.

Aged↗
PubMed1992

Post-irradiation somnolence syndrome in an adult patient following allogeneic bone marrow transplantation.

Neurologic disturbances are common following the intensive chemotherapy and radiotherapy of bone marrow transplantation (BMT) conditioning regimens. The somnolence syndrome, which occurs in most children treated for leukemia with prophylactic cranial irradiation, has previously not been reported following BMT. This syndrome consists of transient lethargy, irritability, headaches, low grade fevers, gastrointestinal disturbances and depression. We report the case of a 38-year-old female with acute non-lymphocytic leukemia who developed symptoms typical of the somnolence syndrome 8 weeks following 1320 cGy total body irradiation and cyclophosphamide conditioning. Encephalographic findings were consistent with the syndrome, and no additional infectious or metabolic disorders could be identified. As predicted by the pediatric experience, the symptoms were transient, resolving following steroid and anti-depressant therapy. Among patients undergoing radiation based conditioning regimens, especially those not receiving concurrent steroid therapy, the appearance of post-transplantation somnolence may be an expression of this syndrome.

Adult↗
PubMed1990

Clonal studies in the myelodysplastic syndrome using X-linked restriction fragment length polymorphisms.

We used the X-linked restriction fragment length polymorphism (RFLP)-methylation strategy to study the clonal basis of the myelodysplastic syndrome (MDS) in seven patients. RFLP-methylation analysis was performed on cell populations from bone marrow (BM) aspirates and peripheral blood using probes specific for the hypoxanthine phosphoribosyltransferase (HPRT) or phosphoglycerate kinase (PGK) gene regions. Density gradient centrifugation methods were used to separate granulocytes and monocytes, and T lymphocytes were positively selected by CD2 (a pan-T marker) immunoconjugated magnetic beads. Cell populations from BM aspirates in 6 of the 7 patients with MDS showed a monoclonal pattern of X-inactivation. The neutrophilic and T-lymphocytic cell fractions were analyzed in 4 of the 6 patients, and the monocytic cell fraction in one of these, and all fractions analyzed showed a similar monoclonal pattern. In 2 of the latter 4 patients, both of whom had normal karyotypes, DNA from a skin biopsy showed a polyclonal pattern. Our data suggest that MDS is a clonal disorder, even in the absence of detectable cytogenetic abnormalities, and that the abnormal clone is capable of myeloid, monocytic, and lymphoid differentiation.

Bone Marrow↗
PubMed1990

Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia.

Most of human follicular lymphomas possess the t(14;18) chromosome translocation that juxtaposes the IgH gene to the 3' region of bcl-2 in a head-to-tail configuration. Here we show that the rearrangement of the bcl-2 gene occurs in a significant fraction (approximately of 10%) of B cell CLL. In all cases analyzed, breakpoints on chromosome 18 clustered at the 5' flanking region of the bcl-2 gene, and no rearrangements were found at the major or minor breakpoint clustering region (3' region of bcl-2 gene) typical of the t(14;18) chromosome translocation. All of the rearranged bcl-2 genes were juxtaposed with the Ig lambda or K genes in a head-to-head configuration. These results imply that the bcl-2 gene is preferentially linked to the IgL genes in CLL and could function in leukemogenesis.

Base Sequence↗
PubMed1990

A new murine monoclonal antibody for the diagnosis of erythroleukemia.

The authors have developed a murine monoclonal antibody, RC-82.4, against an antigen expressed by a human erythroleukemia cell line OCI-MIR. The antibody reacts with an antigen expressed by proerythroblasts, normoblasts, and some reticulocytes but not expressed in erythrocytes, granulocytes, monocytes, megakaryocytes, plasma cells, or lymphocytes. The authors have established an immunocytochemical method for studying bone marrow smears with RC-82.4. By studying bone marrow smears from 11 patients with M-6 erythroleukemia and 104 patients with various other hematologic and nonhematologic malignancies, the authors have found that RC-82.4 has great sensitivity and specificity in recognizing erythroid differentiation in blasts. The authors have used RC-82.4 and antihemoglobin antibodies to identify erythroblasts in acute and secondary acquired cases of erythroleukemia that would have been unclassifiable by morphologic and all other conventional cytochemical and immunocytochemical criteria.

Adult↗
PubMed1990

Clinical correlates of distinct immunophenotypic and histologic subcategories of lymphocyte-predominance Hodgkin's disease.

Histologic and paraffin immunohistologic studies were carried out on 32 patients with lymphocyte-predominance Hodgkin's disease (LPHD) seen from 1970 through 1982. While nodular histology was accurately predictive of B-cell phenotype (Leu M1 -/L26+), diffuse histology corresponded to either B-cell or Hodgkin's (Leu M1 +/L26-) phenotype, not invariably predictable even when attention was paid to subtle paragranuloma cytology. Clinical characteristics were compared between histologic (diffuse v nodular) and immunophenotypic (Leu M1 +/L26-, Hodgkin's phenotype, v Leu M1 -/L26+, B-cell phenotype) subgroups. Ten patients have since died, and the median follow-up of the living patients was 14 years (range, 6 to 31). Of the several clinical parameters compared, only axillary nodal presentation was strongly associated with both B-cell phenotype and nodular histology, while male predominance related more to B-cell phenotype than nodular histology. No significant difference in overall survival or relapse rate was apparent among either the histologic or the immunophenotypic subgroups. However, very late but salvageable relapses were associated with nodular histology. The incidences of secondary malignancies and death from Hodgkin's disease (HD) were also comparable between the subgroups. Although difference in clinical presentation may exist, neither the histologic nor the immunophenotypic subcategories of LPHD could be demonstrated to correlate with differences in clinical outcome.

Adolescent↗
PubMed1990

CD5-positive B-cell malignancies frequently express cross-reactive idiotypes associated with IgM autoantibodies.

Using monoclonal antibodies (MAb) specific for cross-reactive idiotypes (CRIs) associated with human monoclonal IgM autoantibodies, we examined 57 biopsy specimens that previously had been noted to have immunohistologic features of CD5-positive B-cell small lymphocytic (SL) non-Hodgkin's lymphoma (NHL). Twenty-five lymphoma specimens were noted to be from patients with chronic lymphocytic leukemia (CLL). Eight of thirty-four (24%) immunoglobulin (Ig) kappa light-chain expressing lymphomas reacted with 17.109, a MAb specific for a major CRI encoded by a conserved Ig kappa variable region gene (Vk gene) of the VkIIIb sub-subgroup. All 17.109-reactive tissues and two 17.109-negative specimens were recognized by another MAb specific for VkIIIb framework determinant(s). Seven of all fifty-six (13%) Ig-expressing tumors bound G6, a MAb specific for an autoantibody heavy-chain-associated CRI that is encoded by a conserved antibody heavy chain variable region gene(s) (VHgene) of the VH1 subgroup. All seven G6-positive lymphomas and two G6-negative tumors reacted with Cc1, another MAb specific for a rheumatoid factor heavy-chain-associated CRI. A third autoantibody-heavy-chain-associated CRI, termed Lc1, was expressed by seven (13%) other lymphomas. Finally, a fourth MAb specific for RF heavy-chain-associated CRI, named B6, detected two additional tumors. The expression frequencies of autoantibody-associated CRIs among SL NHL patients without peripheral lymphocytosis did not differ from those noted among patients with CLL but were significantly higher than those observed among patients with NHL of follicular center-cell origin. These data imply that the malignant B cells of patients with either CD5-positive B-cell SL NHL or CLL express a restricted set of Ig V genes that have not substantially diversified from the germline DNA.

Antibodies, Monoclonal↗
PubMed1990

The location of the Philadelphia chromosomal breakpoint site and prognosis in chronic granulocytic leukemia.

Chronic granulocytic leukemia (CGL) is associated with a reciprocal translocation between chromosomes 9 and 22. The breakpoint sites on chromosome 22 are clustered in a limited region known as the major breakpoint cluster region (Mbcr). This region is approximately 5.8 Kb long and can be arbitrarily subdivided into five zones (1 through 5 from the 5' towards the 3' end) as defined by the particular sites of three restriction endonucleases. Using Southern blot analysis with two DNA probes, one spanning both the 5' and 3' regions of the Mbcr while the other only the 3' region, we mapped the precise location of the chromosomal breakpoints within the Mbcr in 62 patients with CGL and examined possible clinical correlations. There were 39 patients with 5' breakpoints (zones 1-3) and 23 patients with 3' breakpoints (zones 4 and 5). We found no correlation between the clinical phase of the disease at last followup and breakpoint distributions. The distributions of chronic phase duration (CPD) and survival were similar between patients with 5' breakpoints (median CPD = 4.0 years) and those with 3' breakpoints (median CPD = 5.2 years). Presenting clinical features and the rates of lymphoblastic transformation were also similar among the subgroups. Our data suggest that the precise location of the breakpoint within the Mbcr in CGL may not have clinical relevance.

Blast Crisis↗
PubMed1989

Adult-onset cyclic bicytopenia: a case report and review of treatment of cyclic hematopoiesis.

A unique case of adult-onset synchronous cyclic neutropenia and thrombocytopenia occurring at six-week intervals is presented. Periods of cytopenia were associated with fever, myalgias, gastrointestinal symptoms, and mild mucocutaneous bleeding. Alternate-day steroid treatment failed to correct the periodic fluctuations in peripheral blood counts but ameliorated symptoms during cytopenia. The treatment of cyclic hematopoiesis is reviewed.

Agranulocytosis↗
PubMed1989

Steroid-responsive pure red cell aplasia associated with natural killer cell lymphocytosis.

A patient with pure red cell aplasia and expansion of the peripheral blood natural killer (NK) cell population is described. Despite normal absolute and differential leukocyte counts, NK cells were increased at diagnosis and at relapse. Furthermore, these cells were not morphologically recognizable on the peripheral blood smear examination. A favorable clinical response to glucocorticoid therapy was accompanied by a decrease in NK cells.

Azathioprine↗
PubMed1989

Acute leukemia with abnormal thrombopoiesis and inversions of chromosome 3.

Abnormal thrombopoiesis has been described in acute leukemias associated with inv(3) (q21q26.2) or t(3;3)(q21;q26.2). We reviewed 13 patients seen at the Mayo Clinic since 1979 with inversions of chromosome 3 or related abnormalities; 12 acquired and one constitutional. The patient with the constitutional abnormality had an inv(3)(p21q29) and mild leukocytosis and thrombocytosis. Among the 12 patients with acquired abnormalities, five had inv(3) (q21q26.2), three had t(3;3)(q21;q26.2), one had del(3)(q12q21), one had ins(6;3) (p21;q21q26.2), one had inv(3)(p21q12), and one had r(3)(p?21q?21). Each of these patients developed acute leukemia; eight had antecedent myelodysplastic syndrome, eight presented with platelet counts greater than 100 x 10(3)/microliters, and six had atypical megakaryocytic hyperplasia. Five patients had ringed sideroblasts in their marrow, an antecedent refractory anemia with ringed sideroblasts, or erythroleukemia. Seven patients received chemotherapy but showed no response. From the time of chromosome study, the median duration of survival was 4 months. Our results suggest that 1) although abnormal megakaryocytopoiesis is observed in patients with inv(3)(q21q26.2), multiple hematopoietic lineages are also involved in the neoplastic process; 2) an antecedent myelodysplastic syndrome is common in acute leukemia with inv(3) or related abnormalities; 3) affected patients have a poor survival and are resistant to conventional chemotherapy; and 4) abnormal megakaryocytopoiesis in acute leukemia may also be associated with pericentric inversions of chromosome 3.

Acute Disease↗
PubMed1989

Chronic myelomonocytic leukemia: natural history and prognostic determinants.

A retrospective clinical review of 41 patients with chronic myelomonocytic leukemia revealed a median age of 66 years and a male:female ratio of 2.4:1. The disease was preceded by a myelodysplastic syndrome of a different subtype in 24% of the patients and transformed into acute leukemia in 24%. Splenomegaly was present in 54% of the patients and reached massive proportions in 24%. Chromosomal abnormalities occurred in 34% of those studied, most commonly in the younger age group; the most frequent were trisomy 8, monosomy 7, and deletions involving the long arms of chromosomes 20 and X. Polyclonal hypergammaglobulinemia was detected in 47% of the patients in whom serum protein electrophoresis was done. The median survival was 3 years. With use of univariate analysis, the statistically significant prognostic determinants were hemoglobin level, the "modified Bournemouth score," and bone marrow blast cell percentage. When these factors were subjected to a multivariate analysis, only bone marrow blast cell percentage was an independent prognostic determinant. Orally administered hydroxyurea controlled leukocytosis and splenomegaly in some patients without affecting the overall prognosis.

Adult↗