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A Tefferi

Publications and source records attributed to A Tefferi.

At least 37 records · Page 2Linked to original sources
PubMed2004

Bone marrow mast cell immunophenotyping in adults with mast cell disease: a prospective study of 33 patients.

The aberrant co-expression of CD2 and CD25 antigens is the immunophenotypic hallmark of neoplastic mast cells, and has been consistently identified on bone marrow mast cells from patients with indolent mast cell disease (MCD). We prospectively analyzed the bone marrow mast cell immunophenotype by multiparametric flow cytometry (FC) for 33 MCD cases, to examine the role of CD2 and CD25 expression in establishing diagnosis, detecting histologically occult bone marrow mast cell infiltration, and assessing treatment response. While CD25 was almost uniformly expressed, only 6 of 13 patients with indolent MCD, 1 of 8 with aggressive MCD, 2 of 7 with MCD and an associated hematological disorder, and none of the 2 patients with either mast cell leukemia or smoldering systemic mastocytosis, expressed CD2. One of three patients with cutaneous mastocytosis had an aberrant CD2+/CD25+ mast cell population suggesting histologically occult bone marrow involvement. CD25 expression was lost in one patient who achieved complete histologic remission with therapy, but not in two patients who achieved a partial remission. In conclusion, CD25, but not CD2, is a reliable marker for neoplastic mast cells, and CD25 expression indicates histologically occult bone marrow infiltration and residual disease after therapy.

Adult↗
PubMed2004

Treatment of systemic mast cell disease with 2-chlorodeoxyadenosine.

We used three to six courses of 2-chlorodeoxyadenosine (2-CdA) (2-h infusion at 0.14 mg/kg per day x 5 days) given over a period of 3-36 months to treat four patients with aggressive systemic mast cell disease (SMCD) that was resistant to interferon-alpha (IFN-alpha). Treatment with 2-CdA resulted in a major response in two patients and a good partial response in one other patient (75% overall response). Treatment was well tolerated and duration of remission in responding patients ranges from 2 months to 4+ years since the completion of treatment with 2-CdA.

Adult↗
PubMed2004

Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate.

High-dose chemotherapy and autologous stem cell transplantation are used increasingly to treat patients with light-chain-related amyloidosis (AL). Treatment-related mortality is approximately 15%. To enable more patients to undergo stem cell transplantation, a risk-adapted strategy has been developed to treat with lower chemotherapy doses those patients who are at excessive risk. It is unclear whether reducing the chemotherapy dose in patients at excessive risk of treatment toxicity reduces the overall response. We retrospectively reviewed 171 AL patients who underwent conditioning chemotherapy with stem cell transplantation. The patients comprised two groups: those receiving standard high-dose melphalan and those receiving intermediate-dose melphalan. Responses were categorized as hematologic response, which used criteria for myeloma response. The two groups showed statistically significant differences; the overall response rates were 75% in the high-dose group and 53% in the intermediate-dose group although treatment-related mortality was the same in both groups. Reducing the melphalan dose appeared to render more AL patients eligible for stem cell transplantation but sacrificed an element of response. Methods are needed to reduce treatment-related toxicity so that more patients can receive full-dose conditioning chemotherapy.

Adult↗
PubMed2003

Treatment advances in adult immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by autoantibody-mediated destruction of platelets. The disease generally runs a mild clinical course, though significant morbidity and mortality can occur. Steroids and/or splenectomy are effective in treating the disease in approximately 70% of patients. These treatments have been well established with approximately 50 years of clinical experience. While open splenectomy is the traditional surgical procedure, laparoscopic splenectomy, splenic artery embolization, and splenic irradiation are viable alternatives. For patients who relapse after the above therapies, treatment is more difficult and seldom results in a cure. The goals of therapy involve maintaining a safe platelet count while minimizing toxicities from the treatment. Multiple treatment options exist including corticosteroids, androgens, immunomodulatory drugs, cytotoxic chemotherapy, immunoglobulin preparations, bone marrow transplantation, Helicobacter pylori eradication, and others. While the standard treatment of steroids and splenectomy has changed little over the past decades, a number of promising new therapies on the horizon may soon join the armamentarium upon which the clinician can draw to fight the disease. In this review, we will examine treatment for chronic ITP in adults in the pre-splenectomy, splenectomy, and post-splenectomy settings.

Age of Onset↗
PubMed2003

Imatinib for systemic mast-cell disease.

Imatinib has shown to be effective against malignant disease driven by ckit. We prospectively treated 12 adults with symptomatic systemic mast-cell disease at a dose of either 100 mg or 400 mg per day. Of the ten patients who we could assess for response, five (50%) had a measurable response to the drug, four of whom had important mast-cell cytoreduction and two who had complete clinical and histological remission. In the five patients with eosinophilia, three had complete clinical and haematological remission. The other two, who did not respond to treatment, were the only patients with the ckit D816V mutation. Our results suggest that imatinib either inhibits the growth-promoting role of wild type ckit, or targets an oncogenic kinase.

Adult↗
PubMed2003

Secondary myelodysplastic syndrome and acute myelogenous leukemia are significant complications following autologous stem cell transplantation for lymphoma.

Secondary myelodysplastic syndrome (sMDS) and acute myelogenous leukemia (AML) have been recognized with increasing frequency following autologous stem cell transplantation (ASCT). A retrospective analysis of 230 consecutive patients with Hodgkin's lymphoma (HL, 64) and non-Hodgkin's lymphoma (NHL, 166) who underwent ASCT was conducted to assess the incidence and risk factors for the development of sMDS/AML. At a median follow up of 41 months (range 0.1-177 months), 10 of 230 patients (4.3%) developed sMDS/AML. The 5-year-actuarial incidence of sMDS/AML was 13.1% and 5-year cumulative incidence by competing risk analysis was 4.2%. The median time to development of sMDS/AML was 39.9 months from the time of ASCT (range 12.1-62.0 months). Complex karyotypes at diagnosis of sMDS/AML included structural anomalies and/or loss of chromosome 5 (eight patients), 7 (five patients), 17 (two patients) and 20 (two patients). All patients subsequently died, at a median of 6.8 months (range 0-39.9) from diagnosis of sMDS/AML. Fluorescent in situ hybridization (FISH) analysis for -5/5q- and -7/7q- were normal in all six patients whose pre-ASCT bone marrow was available for testing. Five of the six had samples available for testing at diagnosis of sMDS/AML and all had abnormal FISH results. By univariate statistical analysis, male gender (P=0.01), prior alkylating agents (mechlorethamine for HL, P=0.001 and cyclophosphamide for NHL, P=0.05) and the number of prior treatment regimens (P=0.04) were significantly associated with the development of sMDS/AML. Given the relatively low incidence rate of sMDS/AML, these analyses are primarily exploratory in nature but provide some insight into relevant risk factors and illustrate the risk of developing sMDS/AML after myeloablative conditioning and ASCT for lymphoma.

Adult↗
PubMed2003

In vitro antiproliferative activity of the farnesyltransferase inhibitor R115777 in hematopoietic progenitors from patients with myelofibrosis with myeloid metaplasia.

R115777 is an orally bioavailable farnesyltransferase inhibitor (FTI) that has displayed encouraging activity in patients with acute myeloid leukemia. To determine whether R115777 might exert similar activity in myelofibrosis with myeloid metaplasia (MMM), we evaluated its effects on circulating myeloid progenitor cells from patients with MMM (n=25) using in vitro colony-forming assays. The median R115777 concentrations that inhibited colony formation by 50% were 34 and 2.7 nM for myeloid and megakaryocytic colonies from MMM patients, respectively. Progenitors from normal controls and patients with other myeloproliferative disorders demonstrated similar sensitivity. Since the ras polypeptides are one putative target of FTIs, the potential role of ras effectors was examined by incubating parallel progenitor assays with the phosphatidyl-inositol-3 (PI-3) kinase inhibitor LY294002 and the mitogen-activated protein kinase 1 inhibitor PD98059. MMM progenitor colonies (n=7) were highly sensitive to LY294002 but not to PD98059, implying that the PI-3 kinase pathway may be critical for survival and proliferation of these cells. In addition to indicating that MMM progenitors are sensitive to clinically achievable R115777 concentrations in vitro, these results provide a potential explanation for the thrombocytopenia observed with R115777 during the treatment of other hematologic malignancies.

Adult↗
PubMed2003

Lymphocyte recovery after allogeneic bone marrow transplantation predicts risk of relapse in acute lymphoblastic leukemia.

Allogeneic blood and marrow transplantation (BMT) is curative for many patients with high-risk and relapsed acute lymphoblastic leukemia (ALL). However, relapse is an important cause of post-transplantation failure, and there are no reliable markers to predict relapse. A retrospective review of patients with ALL who underwent matched related allogeneic BMT was carried out to examine whether the rate of lymphocyte recovery after transplantation had any prognostic value in ALL. The absolute lymphocyte count (ALC) at days 21 and 30 after transplantation was obtained for 43 patients who received transplants during an 18-year period. Patients with an ALC of 175 x 10(6)/l or less on day 21 were more likely to relapse than those with ALC greater than 175 x 10(6)/l (relative risk, 4; 95% confidence interval, 1.5-11.2). Patients with slower lymphocyte recovery had significantly lower relapse-free survival than those with faster recovery (P=0.0028). There was also a trend toward poorer overall survival among those with a slow lymphocyte recovery (log-rank test; P=0.028). The rate of lymphocyte recovery is prognostic in patients with ALL undergoing allogeneic BMT, and this should be integrated with other predictors to identify patients at high risk of relapse. Such patients could be considered for interventions aimed at prevention of relapse, including rapid withdrawal of immunosuppressive medication or donor lymphocyte infusion.

Adolescent↗
PubMed2002

Splenectomy for immune thrombocytopenic purpura: long-term results and treatment of postsplenectomy relapses.

Information regarding prognostic determinants of outcome after splenectomy for adult immune thrombocytopenic purpura (ITP) and the management of postsplenectomy relapse is limited. Among 140 adult patients with ITP who had therapeutic splenectomy at our institution, 88% achieved either a complete (platelets > 150 x 10(9)/l) or a partial (platelets > or = 50 x 10(9)/l) response that was sustained for at least 1 month. At 3, 6, and 12 months after splenectomy, time-adjusted complete response rates were 77%, 71%, and 74%, respectively. The 5-year relapse-free survival was 75%; all but three relapses occurred within 2 years of splenectomy. In multivariate analysis, younger age and higher peak postsplenectomy platelet counts were significantly associated with a favorable response to splenectomy. None of several preoperative or perioperative variables was predictive of a relapse after an initial response to splenectomy. Corticosteroids, danazol, vincristine, and cyclophosphamide were often effective in the treatment of patients who were either refractory to or had a relapse after splenectomy. One patient responded to rituximab after not responding to corticosteroids, azathioprine, and vincristine. After a median follow-up of 37.5 months (range: 0-183) from splenectomy, there were 25 deaths, including 2 from postoperative complications, 1 from gastrointestinal bleeding related to thrombocytopenia, and 1 from overwhelming sepsis related to the splenectomized state. The current study provides additional data on both the long-term outcome of splenectomy in adults with ITP and the management of postsplenectomy relapse.

Adolescent↗
PubMed2002

Variations in bone density among persons of African heritage.

The epidemiology of bone loss in populations of African heritage is still poorly known. We compared a convenience sample of 47 African-American (AA) residents of Rochester, Minnesota (32 women, 15 men) and 66 recent immigrants from Somalia (all women) with 684 white subjects (349 women, 335 men) previously recruited from an age-stratified random sample of community residents. Areal bone mineral density (BMD, g/cm(2)) and volumetric bone mineral apparent density (BMAD, g/cm(3)) were determined for lumbar spine and proximal femur using the Hologic QDR 2000 for white subjects and the QDR 4500 for the others; the instruments were cross-calibrated from data on 20 volunteers. Lumbar spine BMD was 18% higher in AA ( p<0.001) and 4% lower in Somali ( p = 0.147) than white women. Femoral neck BMD was 27% higher in AA women but also 11% greater in Somali women (both p<0.001) compared with whites. Lumbar spine BMD was 6% higher ( p = 0.132) and femoral neck BMD 21% higher ( p<0.001) in AA than white men. No Somali men were studied. After correcting for bone size differences, both lumbar spine ( p<0.01) and femoral neck BMAD ( p<0.001) were greater for Somali than white women, but the difference between Somali and AA women persisted. Lumbar spine and femoral neck BMAD values also remained significantly greater for AA women (both p<0.001) and men ( p<0.05; p<0.001) compared with whites. Weight was associated with BMAD at both skeletal sites in all groups, but adjustment for differences in weight did not reduce the discrepancy in BMAD values between Somali and AA women or between the latter group and whites. This heterogeneity among different ethnic groups of African heritage may provide an opportunity for research to better explain race-specific differences in bone metabolism.

Absorptiometry, Photon↗
PubMed2002

Omission of day +11 methotrexate after allogeneic bone marrow transplantation is associated with increased risk of severe acute graft-versus-host disease.

The combination of CYA and short-course MTX is commonly used for GVHD prophylaxis after allogeneic BMT. Severe mucositis and organ dysfunction early after transplantation often lead to omission of the day +11 dose of MTX. To examine whether this omission increases the risk of acute or chronic GVHD, we reviewed 135 allogeneic BMTs performed at our institution in which CYA and short-course MTX prophylaxis were used. Patients receiving less than three doses of MTX and those who died before day +11 were excluded. Of the 123 eligible patients, 84 received all four doses and 39 received three doses, with the fourth dose withheld because of severe mucositis (n = 27) or hepatic or renal dysfunction (n = 12). Acute GVHD of any grade developed in 23 patients (59%) in the three-dose group compared with 57 patients (68%) in the four-dose group (P = 0.33). Chronic GVHD developed in 15 patients (38%) in the three-dose group compared with 31 patients (37%) in the four-dose group (P = 0.87). There was no difference in the overall rate of acute or chronic GVHD between the groups. However, the three-dose group was more likely to develop grade III or IV acute GVHD (12 of 39 (31%) ) compared with the four-dose group (12 of 84 (14%); P = 0.03). Relapse-free survival was similar for the two groups. We conclude that omitting day +11 MTX appears to increase the risk of severe acute GVHD.

Acute Disease↗
PubMed2002

Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia.

Absolute lymphocyte count (ALC) recovery correlates with survival after autologous hematopoietic stem cell transplantation (AHSCT) for patients with multiple myeloma, non-Hodgkin's lymphoma, and metastatic breast cancer. The role of ALC recovery in relationship to clinical outcome after AHSCT in patients with acute myelogenous leukemia is unknown. We analyzed 45 patients who underwent AHSCT at Mayo Clinic, Rochester, Minnesota between 1990 and 2000. The ALC threshold was selected at 500 cells/microl on day 15 post-AHSCT based on our previous studies. Thirty-two females and 13 males were included in the study with a median age of 45 years (range 12-75). The median follow-up was 14 months with a maximum of 129 months. The median overall and leukemia-free survival were significantly better for the 23 patients with ALC at day 15 > or =500 cells/microl compared with 22 patients with ALC <500 cells/microl (not yet reached vs 10 months, P < 0.0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC > or =500 cells/microl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies.

Adolescent↗
PubMed2001

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation in multiple myeloma or non-Hodgkin lymphoma.

Autologous stem cell transplantation (ASCT) improves survival in patients with previously untreated multiple myeloma (MM) and relapsed, chemotherapy-sensitive, aggressive non-Hodgkin lymphoma (NHL). Lower relapse rates seen in allogeneic stem cell transplantation have been related to early absolute lymphocyte count (ALC) recovery as a manifestation of early graft-verus-tumor effect. In ASCT, the relation between ALC recovery and clinical outcomes in MM and NHL was not previously described. This is a retrospective study of patients with MM and NHL who underwent ASCT at the Mayo Clinic between 1987 and 1999. The ALC threshold was determined at 500 cells/microL on day 15 after ASCT. The study identified 126 patients with MM and 104 patients with NHL. The median overall survival (OS) and progression-free survival (PFS) times for patients with MM were significantly longer in patients with an ALC of 500 cells/microL or more than patients with an ALC of fewer than 500 cells/microL (33 vs 12 months, P <.0001; 16 vs 8 months, P <.0003, respectively). For patients with NHL, the median OS and PFS times were significantly longer in patients with an ALC of 500 cells/microL or more versus those with fewer than 500 cells/microL (not reached vs 6 months, P <.0001; not reached vs 4 months, P <.0001, respectively). Multivariate analysis demonstrated day 15 ALC to be an independent prognostic indicator for OS and PFS rates for both groups of patients. In conclusion, ALC is correlated with clinical outcome and requires further study. (Blood. 2001;98:579-585)

Actuarial Analysis↗
PubMed2001

Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis.

Current therapeutic options for myeloid metaplasia with myelofibrosis (MMM) are limited. A pilot study was conducted of autologous peripheral blood stem cell (PBSC) collection in 27, followed by transplantation in 21 patients with MMM. The median age was 59 (range 45-75) years. PBSCs were mobilized at steady state (n = 2), after granulocyte colony-stimulating factor (G-CSF) alone (n = 17), or after anthracycline-cytarabine induction plus G-CSF (n = 8). A median of 11.6 x 10(6) (range 0 to 410 x 10(6)) CD34(+) cells per kilogram were collected. Twenty-one patients then underwent myeloablation with oral busulfan (16 mg/kg) and PBSC transplantation. The median times to neutrophil and platelet recovery after transplantation were 21 (range 10-96) and 21 (range, 13 to > or = 246) days, respectively. Five patients received back-up PBSC infusion because of delayed neutrophil or platelet recovery. The median follow-up is 390 (range 70-1623) days after transplantation, and the 2-year actuarial survival is 61%. After transplantion, 6 patients died: 3 of nonrelapse causes (1 within 100 days of PBSC infusion) and 3 of disease progression. Erythroid response (hemoglobin > or = 100 g/L [10 gm/dL] without transfusion for > or = 8 weeks) occurred in 10 of 17 anemic patients. Four of 8 patients with a platelet count less than 100 x 10(9)/L (100 000/microL) responded with a durable platelet count more than 100 x 10(9)/L (100 000/microL). Symptomatic splenomegaly improved in 7 of 10 patients. It is concluded that (1) PBSC collection was feasible and stable engraftment occurred after transplantation in most patients with MMM, (2) myeloablation with busulfan was associated with acceptable toxicity, (3) a significant proportion of patients derived clinical benefit after treatment, and (4) further investigation of this novel approach is warranted. (Blood. 2001;98:586-593)

Aged↗
PubMed2001

Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes.

Acquired pure red cell aplasia (PRCA) can be associated with lymphoproliferative disease of granular T lymphocytes (T-LDGL), also known as T-cell large granular lymphocyte leukemia. Fifteen adult patients with PRCA associated with T-LDGL comprise this study. Neutropenia and rheumatoid arthritis were uncommon. All patients responded to immunosuppressive therapy. The 2 most commonly used treatments were prednisone and cyclophosphamide +/- corticosteroids, producing overall response rates of 50% and 60%, respectively. Treatment with cyclophosphamide was associated with a more durable remission (median, 60 versus 7.5 months). After a median follow-up of 67 months, 2 patients died of treatment-related complications, one from myelodysplasia and another from cyclosporine-induced renal failure. The clinical course and treatment responses of PRCA associated with T-LDGL in this series were similar to the general group of PRCA. Because T-LDGL is frequently underdiagnosed, it is likely that a significant proportion of idiopathic or primary PRCA is in fact secondary to T-LDGL.

Adrenal Cortex Hormones↗
PubMed2001

Clinical correlates of splenic histopathology and splenic karyotype in myelofibrosis with myeloid metaplasia.

Splenic extramedullary hematopoiesis is an integral component of myelofibrosis with myeloid metaplasia (MMM) and may be classified into 3 distinct histologic patterns of infiltration by myeloid precursors: diffuse, nodular, and a predominance of immature granulocytes. These 3 histologic patterns occurred in 121 (56.8%), 75 (35.2%), and 17 (8%), respectively, of 213 patients with MMM who underwent splenectomy at a single institution. In general, karyotypic findings in splenic tissue (n = 92) were similar to those seen in the bone marrow. The histologic pattern of immature granulocyte predominance, the presence of microscopic splenic infarcts (26 patients), or the detection of an abnormal splenic karyotype (52 patients) was significantly associated with decreased postsplenectomy survival. These adverse features were also associated with characteristics of advanced disease. These observations support the bone marrow origin of the myeloid progenitor pool in the spleen of patients with MMM and suggest a prognostic value for splenic histopathology and karyotype. (Blood. 2001;97:3665-3667)

Bone Marrow Cells↗