Clinical and bone marrow effects of interferon alfa therapy in myelofibrosis with myeloid metaplasia.
Explore the source record for details and available documents.
Blood Cell Count↗
Biomedical subjects
A Tefferi
Publications and source records attributed to A Tefferi.
Long-term use of anagrelide in young patients with essential thrombocythemia.
Anagrelide is a novel platelet-lowering agent that has recently been approved for use in essential thrombocythemia (ET) and related disorders. Short-term drug efficacy and toxicity data have previously been presented. The purpose of this study was to obtain additional information regarding long-term anagrelide use. This is a retrospective series of 35 young patients (17 to 48 years) with ET who received anagrelide treatment before 1992. Initial drug dosage ranged between 1 and 10 mg/d, and the median maintenance dosage was 2.5 mg/d. The overall initial response rate of 94% included 74% complete remissions and 20% partial remissions. Of the 33 responding patients, 27 (82%) remained on anagrelide therapy for a median of 10.8 years (range, 7 to 15.5). Of these, 66% maintained a complete and 34% a partial remission over the study period. In general, the reporting of somatic side effects decreased over time, and anemia was the only new side effect that emerged after long-term therapy. Eight patients (24%) experienced a more than 3 g/dL decrease in hemoglobin level. Despite active therapy, 20% of the patients experienced a total of 10 thrombotic episodes, and a similar proportion experienced major hemorrhagic events. All thrombohemorrhagic complications occurred at a platelet count of more than 400 x 10(9)/L. It is concluded that long-term treatment of ET with anagrelide is associated with decreased reporting of initial side effects and the development of mild-to-moderate anemia. Complete normalization of platelet counts may be needed to minimize residual thrombohemorrhagic risk during therapy. (Blood. 2001;97:863-866)
Adolescent↗
Treatment of systemic mast-cell disease with cladribine.
Explore the source record for details and available documents.
Antineoplastic Agents↗
The pathogenesis of chronic myeloproliferative diseases.
Chronic myeloproliferative disorders are operationally classified to include essential thrombocythemia, polycythemia vera, and agnogenic myeloid metaplasia. In most cases, clonal hematopoiesis, involving all 3 myeloid lineages, can be demonstrated. However, the underlying molecular lesions that are responsible for disease initiation and progression remain elusive. There are ongoing efforts to clarify the pathogenetic role of cytokines, bone marrow stromal cells and molecules, and intracellular aberrations in either signal transduction or apoptosis. This review discusses some of the current and past observations regarding the pathogenesis of chronic myeloproliferative disorders.
Bone Marrow Cells↗
A bone marrow report of absent stainable iron is not diagnostic of iron deficiency.
The absence of stainable iron in a bone marrow aspirate is widely considered to be diagnostic of iron deficiency anemia (IDA). We re-evaluated this concept by studying a cohort of 108 consecutive bone marrow specimens from an unselected series of patients who were seen at a hematology clinic and in whom iron stores were reported as being absent. A review of the pathologic reports revealed 19 inadequate specimens and 15 with decreased, but not absent, iron stores. Thus, only 74 of the 108 cases had been accurately reported. In 37 of these cases, adequate clinical and laboratory data were available and allowed further analysis. In 18 patients, careful review of patient history, physical examination, results of endoscopic procedures, and follow-up information failed to suggest the presence of IDA (group A). The review process in the remaining 19 patients suggested the possibility of IDA (group B). Significant differences between groups A and B were observed in serum ferritin (P = 0.001) and red blood cell mean corpuscular volume (P = 0.004). In contrast, the two groups did not differ significantly in hemoglobin concentration, serum iron, total iron-binding capacity, transferrin saturation, or erythrocyte sedimentation rate. These observations suggest that a pathology report of absent bone marrow hemosiderin may be inaccurate in more than 30% of cases and, even when accurate, may not necessarily signify the presence of IDA. Measurement of the serum ferritin level is needed to confirm a clinical diagnosis.
Aged↗
Spontaneous pneumomediastinum and subcutaneous emphysema complicating bronchiolitis obliterans after allogeneic bone marrow transplantation--case report and review of literature.
Chronic graft-versus-host disease occurring in the setting of allogeneic bone marrow transplantation (BMT) can affect many organ systems, is a cause of significant morbidity, and contributes to late deaths. Bronchiolitis obliterans is a form of obstructive airway disease; when seen in the post-BMT setting, it is considered a manifestation of chronic graft-versus-host disease. Air-leak syndromes including pneumothoraces, pneumomediastinum and subcutaneous emphysema are rare complications of bronchiolitis obliterans. Here we describe a patient who developed pneumomediastinum, pneumopericardium, subcutaneous emphysema and pneumothorax secondary to severe bronchiolitis obliterans complicating the post bone marrow transplantation course.
Adult↗
Chronic myeloid disorders: Classification and treatment overview.
Chronic myeloid disorders (CMD) are collectively characterized by monoclonal myeloproliferation that involves multiple lineages, retains a variable degree of cellular maturation, and has the potential to undergo clonal evolution. However, monoclonal hematopoiesis is neither essential nor specific to CMD. Morphologic and cytogenetic characteristics allow a working classification of these disorders that is clinically useful. There are four major divisions: chronic myeloid leukemia (CML), which is easily identified by the presence of the Philadelphia chromosome (or its molecular equivalent); the myelodysplastic syndromes (MDS), which are characterized by trilineage dysplasia; chronic myeloproliferative diseases (CMPD), which include essential thrombocythemia, polycythemia vera, and agnogenic myeloid metaplasia (AMM); and atypical CMD, which includes chronic neutrophilic leukemia, chronic eosinophilic leukemia, mast cell disease, and myeloid processes that display overlapping features of MDS and CMPD (hybrid CMD). In CMPD, a diagnosis of polycythemia vera requires evidence of an erythropoietin-independent increase in red blood cell mass; the diagnosis of both AMM and essential thrombocythemia requires the exclusion of reactive causes of bone marrow fibrosis and thrombocytosis, respectively. In addition, the Philadelphia chromosome, increased red blood cell mass, and dyserythropoiesis should also be absent. Semin Hematol 38(suppl 2):1-4.
Bone Marrow Diseases↗
Amifostine alone and in combination with erythropoietin for the treatment of favorable myelodysplastic syndrome.
Ten anemic patients with favorable myelodysplastic syndrome (MDS) were first treated with two 5-week courses of amifostine alone (each course consisted of 200 mg/m(2) of the drug given intravenously three times a week for 3 weeks), followed by an additional two courses combined with subcutaneous erythropoietin (EPO) (150 U/kg, three times a week for 8 weeks). The study patients either had previously failed to respond to treatment with EPO or had pretreatment serum EPO levels of more than 100 mU/ml. None of the patients experienced a complete or partial response in anemia or other cytopenias. We conclude that amifostine alone or in combination with EPO has limited therapeutic activity in MDS.
Aged↗
Recent progress in the pathogenesis and management of essential thrombocythemia.
In the last decade, the diagnosis of essential thrombocythemia (ET) has been refined by appreciation of the occurrence of karyotypically occult but molecularly evident chronic myelogenous leukemia and morphologically subtle myelodysplastic syndrome (MDS) and cellular-phase agnogenic myeloid metaplasia (AMM). Although ET continues to be defined by the presence of nonreactive thrombocythemia that is not accounted for by another chronic myeloid disorder, recent studies of clonality and other laboratory parameters have suggested clinically relevant biologic heterogeneity among affected patients. Furthermore, randomized, prospective, and controlled retrospective data have provided additional clinical information that has resulted in the development of risk categories and risk-adjusted treatment recommendations.
Adult↗
Myelodysplasia with fibrosis: a distinct entity?
Explore the source record for details and available documents.
Bone Marrow↗
Radiation therapy for symptomatic hepatomegaly in myelofibrosis with myeloid metaplasia.
OBJECTIVE: To describe the experience with liver irradiation in advanced cases of myelofibrosis with myeloid metaplasia (MMM). METHODS: Over a 20-yr period, 14 patients with MMM were treated with a total of 25 courses of liver, abdominal, or abdominal and pelvic irradiation for symptomatic hepatomegaly with (5 patients) or without (9 patients) ascites. All 14 patients had advanced disease and 11 (79%) had previous splenectomy. The median radiation therapy (RT) dose per course was 150 cGy (range 50-1000) administered at a median of six fractions. Four patients received two to six courses. RESULTS: Twelve of the 14 patients (86%) had a transient (median 3 months) subjective response from RT. However, in only 35% of these was there a transient (median 3 months) decrease in palpable liver size. Four of the five patients with ascites experienced a short-term response from RT. Eight of the 13 patients suitable for evaluation (62%) had treatment-associated cytopenia, often in the form of anemia and/or thrombocytopenia. At last follow-up, 10 patients (71%) had died after a median of 7 months (range 0.1-23) and 4 were alive at 3, 20, 33, and 57 months after RT. CONCLUSIONS: Low-dose abdominal RT for symptomatic hepatomegaly or ascites associated with advanced-stage MMM is myelosuppressive and provides only temporary and mainly subjective and short-lived relief.
Abdomen↗
A single institutional experience with 43 pregnancies in essential thrombocythemia.
OBJECTIVES: We describe the periconception circumstances and outcome of 43 consecutive pregnancies in an unselected group of young women with essential thrombocythemia (ET). PATIENTS AND METHODS: We retrospectively studied 74 consecutive cases of young women with ET seen at our institution, among whom 43 pregnancies occurred in 20 patients. RESULTS: Of the 43 pregnancies, 22 (51%) were successful (21 term and 1 preterm live births) and 21 (49%) ended in miscarriages (1 ectopic pregnancy, 2 elective abortions, 16 first-trimester spontaneous abortions, 1 stillbirth at 22 wk, and 1 abruptio placentae at 33 wk). Management of ET at the time of conception included either no specific therapy (16 cases) or the use of aspirin alone (24 cases), a cytoreductive agent (2 cases), or heparin (1 case). There were no significant differences with respect to platelet count or the effect of treatment with aspirin, either at the time of conception or during the first trimester, among cases of successful pregnancies (22), all miscarriages (21), or first-trimester spontaneous abortions (16). The findings were similar when the analysis was restricted to only first-time pregnancies. In patients with multiple pregnancies, the outcome of a subsequent pregnancy was not predicted by the outcome of the first. In general, in successful cases the last two trimesters were mostly uneventful, with healthy offspring being reported in all cases. CONCLUSIONS: Pregnant patients with ET have an increased risk of first-trimester abortion which is not predictable by preconception platelet count or aspirin therapy. In addition, our experience does not support the use of prophylactic platelet apheresis during delivery.
Abortion, Induced↗
Prophylaxis of graft-versus-host disease with cyclosporine-prednisone is associated with increased risk of chronic graft-versus-host disease.
To determine the effect of two different graft-versus-host disease (GVHD) prophylactic regimens--cyclosporine with short course of methotrexate (CYA-MTX) and cyclosporine with prednisone (CYA-PRED)--on the incidence of chronic GVHD (cGVHD), we retrospectively reviewed the outcomes of 196 consecutive allogeneic related blood and marrow transplants performed at our institution utilizing one of these regimens. CYA-PRED was given to patients who were transplanted more recently because of concern about the increased risk of veno-occlusive disease of the liver, increased mucositis, and slower engraftment in patients receiving CYA-MTX. Prophylaxis with CYA-PRED was associated with a higher risk of development of cGVHD (risk ratio (RR) 3.5; 95% confidence intrerval (CI), 2.2-5.4). The proportion of patients with extensive disease among those developing cGVHD was higher in the CYA-PRED group (71%) than in the CYA-MTX group (57%), although this difference was not statistically significant. The cumulative probability of extensive cGVHD at 2 years was higher in the CYA-PRED group (RR 4.2, 95% CI, 2.4-7.4). Development of acute GVHD and cytomegalovirus mismatch were independent predictors of increased risk of cGVHD. We conclude that GVHD prophylaxis with CYA-PRED is associated with a higher overall rate of cGVHD compared to CYA-MTX. The type of GVHD prophylaxis should be considered when comparing the incidence of cGVHD reported in different studies.
Adolescent↗
Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation.
From 1987 to 1998, 19 of 416 patients (4.6%) who underwent autologous hematopoietic stem cell transplantation experienced peri-engraftment (within 5 days of neutrophil recovery) respiratory distress syndrome (PERDS) not attributable to infection, fluid overload, or cardiac dysfunction. The median time from stem cell infusion to onset of PERDS was 11 days (range 4-25). Risk of PERDS or its outcome was not predicted by any pre- or peri-transplant clinical or laboratory feature. The respective median white blood cell and platelet counts at first symptoms were 1.3 x 10(9)/l and 25 x 10(9)/l. No patients had an infectious etiology by bronchoalveolar lavage. Six of the 19 patients had alveolar hemorrhage, which was significantly correlated with high neutrophil count. PERDS was directly implicated in four deaths (21%). Eleven patients received high-dose corticosteroid therapy, including five of the six who required mechanical ventilation. Ten of these patients experienced clinical improvement, which occurred within 24 h in five. The rapid response to corticosteroid treatment and the fact that such therapy was delayed until after intubation in all the mechanically ventilated cases point to a therapeutic benefit.
Adolescent↗
Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation.
Pulmonary complications develop in 30-60% of hematopoietic stem cell transplants (HSCT). The main, late onset, non-infectious complications include Bronchiolitis obliterans (BO), Bronchiolitis obliterans organizing pneumonia (BOOP), and idiopathic pneumonia syndrome (IPS). BO and BOOP occur almost exclusively in allogeneic HSCT, and have 61% and 21% mortality rates, respectively. BOOP responds favorably to corticosteroids. IPS has less than 15% 1-year survival.
Bronchiolitis Obliterans↗
Development of hepatic veno-occlusive disease after Mylotarg infusion for relapsed acute myeloid leukemia.
Mylotarg (gemtuzumab zogamicin) is a conjugated monoclonal antibody that has recently become available for use in patients with relapsing or refractory acute myeloid leukemia. Reversible hepatotoxicity is common after administration. We describe the first report of hepatic veno-occlusive disease (HVOD) developing after Mylotarg infusion in a patient who underwent hematopoietic stem cell transplantation 8 months earlier. Certain antineoplastic agents have been implicated as a cause of HVOD, but the disease is most commonly seen within 30 days after hematopoietic stem cell transplantation. The possible association between Mylotarg infusion and HVOD is discussed.
Aged↗
Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia.
Allogeneic BMT is potentially curative for patients with acute myelogenous leukemia (AML) in first remission. However, many patients relapse after transplantation. Various immunotherapeutic options have been attempted with variable success in preventing relapse. Early identification of patients at high risk for relapse could allow prompt intervention. We examined the effect of slow lymphocyte recovery after sibling-matched allogeneic BMT on the risk of relapse in patients with AML. We also examined the effect of prednisone-containing GVHD prophylaxis on the rate of lymphocyte recovery. Patients with absolute lymphocyte count (ALC) <150 x 10(6)/l by day +30 had a 3.5-fold higher risk of relapse (P = 0.0088) and a lower overall survival (P = 0.0079) than patients with a higher ALC. We did not find correlation between lymphocyte count determined earlier in the post-transplantation course (day +21) and the risk of relapse. Patients receiving prednisone had a significantly lower ALC at day +30 than those who did not receive prednisone (289 vs 549 x 10(6)/l, P = 0.002). We conclude that a slow lymphocyte recovery after allogeneic BMT for AML is strongly predictive of subsequent relapse and that the type of GVHD prophylaxis should be considered when analyzing lymphocyte recovery.
Adolescent↗
Charcoal hemofiltration for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.
Hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT) results in considerable morbidity and mortality. No therapy has been shown to be uniformly effective. Several studies have highlighted the pivotal role of endothelial injury and the hemostatic system in the pathogenesis of HVOD. Charcoal hemofiltration has been shown to be effective for adsorbing circulating bilirubin and other protein-bound toxins and for supporting patients in hepatic failure. We describe two adult patients with severe, biopsy-proven HVOD (peak bilirubin levels, more than 50 mg/dl in both cases) after HSCT who were successfully treated with charcoal hemofiltration after other treatments failed (including defibrotide in one patient). Both patients were heavily treated before they underwent either autologous (melphalan and total body irradiation conditioning) or allogeneic (cyclophosphamide and total body irradiation conditioning) HSCT. Additional studies are warranted to confirm this preliminary observation and investigate the mechanism of action.
Adult↗