Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.
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PMID:Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma. 1023 39

The antigen CD33 is expressed on blast cells in 80% to 90% of acute myeloid leukemia (AML) cases but, importantly, is not expressed on pluripotent hematopoietic stem cells or on nonhematologic cells. Gemtuzumab ozogamicin (CMA-676) uses a recombinant humanized anti-CD33 monoclonal IgG4 antibody to deliver the potent cytotoxin, calicheamicin, into cells. Three multicenter trials have evaluated the efficacy and safety of gemtuzumab ozogamicin as a single agent in 142 patients with CD33+ AML in untreated first relapse. The median age was 61 years (range, 22 to 84 years), none had prior myelodysplasia, and all had had a first complete remission lasting > or = 3 months. Two doses of 9 mg/m2 were given 14 days apart by 2-hour intravenous infusion. The overall response rate was 30% (ie, < or = 5% blasts remaining in the bone marrow, neutrophils > or = 1,500/microL, and red blood cell and platelet transfusion independence). There was no significant difference in response rate between patients less than 60 years of age and those > or = 60 years old (34% v 26%, respectively) or between patients whose first remission had lasted less than 12 months or > or = 12 months (28% v 32%, respectively). Overall survival was 31% at 1 year; median survival was 5.9 months. Median relapse-free survival was 6.8 months. An infusion-related syndrome (chills, fever, rigors, nausea, hypotension, and pain) was common. Severe myelosuppression occurred in all patients, but severe mucositis (4%) and infections (23%) were relatively infrequent. Severe hyperbilirubinemia (23%) and elevated hepatic transaminases (18%) were usually transient. Among all 142 patients, the median total hospitalization was 24 days; 16% of patients required < or = 7 days in hospital. Additional studies are currently evaluating gemtuzumab ozogamicin in combination with, or as an alternative to, other standard AML chemotherapy.
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PMID:Current use and future development of gemtuzumab ozogamicin. 1147 94

A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodysplastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors.
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PMID:Pneumocystis carinii pneumonia in patients with malignant haematological diseases: 10 years' experience of infection in GIMEMA centres. 1197 21

Antithymocyte globulin (ATG) is used commonly in patients with severe aplastic anemia and those undergoing renal transplant. Its utility also is being explored in the treatment of myelodysplastic syndrome, conditioning regimens for hematopoietic stem cell transplant, and prophylaxis of graft-versus-host disease. As indications for ATG expand, knowledge regarding its administration and management of associated toxicities is needed. These toxicities range from life-threatening anaphylaxis associated with the infusion to flu-like symptoms that occur one to two weeks after the infusion. Adverse effects are classified according to the severity and system impacted. Mild toxicities respond to comfort measures and include fever, chills, urticarial rash, and vomiting. Moderate toxicities require acute interventions and include fluid-responsive hypotension, nonischemic chest pain, and reversible oxygen desaturation. Severe toxicities require intensive support and include those refractory to earlier intervention. Management of these toxicities usually is limited to fluid resuscitation and noninvasive monitoring. Occurrence of infusion-related toxicities may require premature discontinuation of therapy. Therefore, an educated healthcare team and interdisciplinary clinical management guidelines are important to ensure the safe administration and complete course of ATG.
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PMID:Management of patients receiving antithymocyte globulin for aplastic anemia and myelodysplastic syndrome. 1563 53

DT(388)IL3 fusion protein containing the catalytic and translocation domains of diphtheria toxin fused to human interleukin 3 was administered in an inter-patient dose escalation trial by 15 min i.v. infusions every other day for up to 6 doses to patients with chemo-refractory acute myeloid leukemia (AML) and myelodysplasia (MDS). The maximal tolerated dose was >12.5 microg/kg/dose. Transient grade 3 transaminasemia and grade 2 fevers, chills, hypoalbuminemia, and hypotension occurred. Peak DT(388)IL3 levels correlated with dose and day of administration but not antibody titer. Anti-DT(388)IL3 antibodies developed in most patients between day 15 and 30. Of 40 evaluable AML patients, 1 had a CR (8 months) and 1 had PR (3 months). Of 5 MDS patients, 1 had a PR (4 months). Because of the prolonged infusion schedule, many patients failed to receive six doses. DT(388)IL3 produces remissions in patients with relapsed/refractory AML and MDS with minimal toxicities, and alternate schedules of administration are needed to enhance the response rate.
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PMID:Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia. 1829 33

A multi-institutional, phase 1 dose-escalation trial of lintuzumab (humanized anti-CD33 antibody; SGN-33, HuM195) was performed in patients with CD33-positive myeloid malignancies. In this study, higher doses than previously tested and prolonged duration of treatment for responding patients were evaluated. Over the dose range of 1.5-8 mg/kg/week, lintuzumab was well tolerated, and a maximum tolerated dose was not defined. The most common adverse event was transient chills with the initial lintuzumab infusion (39%). Responses were observed in 7 of 17 patients with acute myeloid leukemia: morphologic complete remission (n = 4), partial remission (n = 2), and morphologic leukemia-free state (n = 1). Of 14 patients with myelodysplastic syndrome or myeloproliferative diseases, 1 patient had major hematologic improvement and 9 patients had stable disease. In contrast to aggressive conventional chemotherapy, lintuzumab was administered in an ambulatory clinic setting with acceptable toxicity.
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PMID:Complete remissions observed in acute myeloid leukemia following prolonged exposure to lintuzumab: a phase 1 trial. 1955 23

A 62-year-old man with refractory leukemia transformed from myelodysplastic syndrome was placed on hydroxyurea (hydroxycarbamide) at a daily dose of 500 mg. Because of insufficient cytoreductive efficacy, the dose was increased to 1,500 mg five days later. Eight days after the initiation of hydroxyurea, the patient started complaining of chills, fever, and vomiting. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were markedly elevated to 5,098 and 3,880 IU/l from 44 and 59 IU/l in one day, respectively. Tests for hepatitis viruses were all negative. With the discontinuation of hydroxyurea, AST and ALT returned to their former levels within two weeks. A drug-induced lymphocyte stimulation test for hydroxyurea was positive with a stimulating index of 2.0. Hepatic dysfunction has been recognized as one of the side effects of hydroxyurea. However, there have been only a limited number of reports demonstrating drug allergy to have a role in hepatic dysfunction accompanied by fever and gastrointestinal symptoms. The findings of our case strongly suggest that all presentations could be explained by drug allergy. Physicians should be mindful of the potential for acute and severe hepatic dysfunction due to allergic reaction against hydroxyurea.
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PMID:[Hydroxyurea (hydroxycarbamide)-induced hepatic dysfunction confirmed by drug-induced lymphocyte stimulation test]. 2449 45

Intravascular large B-cell lymphoma is an extremely rare extranodal lymphoma that proliferates in the lumen of the blood vessels while sparing the organ parenchyma. It usually presents with CNS and skin involvement. A 65-year-old Caucasian female presented with fevers and chills of 3-4 months' duration. Bone marrow biopsy done 3 months prior showed no significant myelodysplasia or lymphoid aggregates. The patient later died due to multiorgan failure. A bone marrow biopsy showed 20-30% CD5+ B cells consistent with infiltrative large B-cell lymphoma. An autopsy performed revealed diffuse intravascular invasion by lymphoma cells. Multiorgan involvement by intravascular B-cell lymphoma is very rare. Based on our literature review and to the best of our knowledge, there are only 5 case reports describing the presentation of this lymphoma with multiorgan failure. The immunophenotypic studies performed revealed that our patient had de novo CD5+ intravascular large B-cell lymphoma which is known to be aggressive with very poor prognosis. Although it is an extremely rare lymphoma, it should be considered as a potential cause of multiorgan failure when no other cause has been identified. A prompt tissue diagnosis and high-dose chemotherapy followed by ASCT can sometimes achieve remission.
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PMID:A Case of De Novo CD5+ Disseminated Intravascular Large B-Cell Lymphoma Presenting as Multiorgan Failure. 2777 3

Herpes zoster is a common disease caused due to varicella zoster virus (VZV) infection with increasing incidence by age. If the patient has a severe, extended, or treatment-recalcitrant course of herpes zoster, this must be a red flag to search for underlying pathologies. Here, we report about a 64-year-old male patient with diabetes, who came to our emergency department because of general malaise, fever, chills, and a pronounced nuchal and facial swelling on the left side. Based on herpetiform-grouped vesicles and yellowish crusts, an impetiginized facial herpes zoster was diagnosed, and combined antiviral and antibiotic treatment was initiated. He was HIV negative. Despite intensified treatment, his situation worsened. We observed blasts in peripheral blood, but bone marrow biopsy was initially denied. Some days later after deterioration of his disease, he accepted further diagnostics. A myelodysplastic syndrome with blast excess (refractory anemia and blast excess II, RAEB II) could be confirmed. The following translocations were detected: t(2;12)(p13; q13) and t(6;9)(p22;q34). REAB II has an unfortunate prognosis. Cytoreductive treatment was initiated by the hematooncologist. Unfortunately, the patient deceased due to septic shock.
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PMID:Severe atypical herpes zoster as an initial symptom of fatal myelodysplastic syndrome with refractory anemia and blast excess (RAEB II). 2865 92

Concurrent presentation of acute promyelocytic leukemia (APL) with other hematologic diseases in the absence of previous chemotherapy or ionizing radiotherapy treatment is very rare. We present a case of simultaneous occurrence of APL with myelodysplastic syndrome (MDS)-related acute myeloid leukemia (AML). A 43-yearold female presented with 3 month of history fatigue, night sweats, chills and pancytopenia. Bone marrow aspirate and biopsy demonstrated 20% myeloid blasts with dysplastic changes admixed with abnormal promyelocytes. Cytogenetic analysis showed tetraploidy and deletion in chromosomes 5q and 7q and polymerase chain reaction showed presence of PML/RARA mRNA transcripts, confirming the presence of concurrent APL and MDS-related AML. Induction chemotherapy with cytarabine and daunorubicin was initiated along with all-trans retinoic acid. This is the first case to be reported in the literature of concurrent occurrence of APL with MDS-related AML. Treatment with 7 + 3 regimen and ATRA was successful in inducing complete remission.
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PMID:Myelodysplasia-related acute myeloid leukemia and acute promyelocytic leukemia: concomitant occurrence of two molecularly distinct diseases. 3028 21


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