摘要:

AbstractThe FAB classification of myelodysplastic syndromes (MDS) has been useful in predicting prognosis; however, additional methods are required to detect patients at high risk for early conversion to acute nonlymphoblastic leukemia (ANLL). Using a panel of monoclonal antibodies to myelomonocytic surface antigens (MMSA) and flow cytometry, we studied bone marrow cells from 26 patients with MDS of all five FAB subtypes. The MMSA studied included la (HLA‐DR), CD11b (Mo1), CD14 (Mo2, My4), CD13 (My7), and CD33 (My9). Marrows were considered 'positive' for a given MMSA if the percentage of reactive cells exceeded the upper limit of the normal range. Twenty‐four of twenty‐six patients (92.3%) were CD13 (My7)+, suggesting that CD13 may serve as a diagnostic marker for MDS. Ten of twelve patients who developed ANLL during a median follow‐up of 44 weeks were la(HLA‐DR)+. The Kaplan‐Meier estimated median time to leukemia (TTL) was 16 weeks for la+ patients and 88 weeks for la– patients (P= 0.004). All six patients who developed ANLL before 16 weeks from diagnosis were la+, while none of the la– patients converted to ANLL before 24 weeks. Nine of thirteen patients with low CD11b (Mo1) expression (53% reactive cells). Kaplan‐Meier estimated TTL was 29 weeks for patients with low CD11b, compared to 160 weeks for patients with high CD11b (P<0.05). Patients who met both criteria, la+ and low CD11b, represented the poorest prognostic subgroup, with median TTL of 13 weeks compared with 88 weeks for the others (P= 0.017), la and CD11b patterns were not specific for MDS subtype, and their expression did not correlate with blast count. These data suggest that MDS patients whose bone marrow cells demonstrate high la (HLA‐DR) and low CD11b (Mo1) expression represent a poor prognostic subgroup with short TTL. These patients may be candidates for early aggressive or invest

ISSN:0361-8609    

DOI:10.1002/ajh.2830430302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe prevalence of anemia in the elderly raises the question of an inappropriate secretion of erythropoietin in response to increased demands. Therefore, the serum erythropoietin concentration of elderly patients (74–95 years) with iron deficiency anemia was measured and compared to that of iron deficiency anemic adults (25–60 years). A lowered erythropoietin secretion in response to anemia was observed in elderly patients in comparison with adults. However, the serum erythropoietin of the anemic elderly was inversely correlated with hemoglobin levels as shown for the anemic adults. The progressive reduction of the renal function observed with aging could explain the decreased capacity of erythropoietin secretion in elderly patie

ISSN:0361-8609    

DOI:10.1002/ajh.2830430303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA subset of hemophilia B patients have a prolonged bovine‐brain prothrombin time. These CRM+patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor × present in the sample. The prothrombin time changed as much as 20 seconds when the factor × concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor × concentrations are k

ISSN:0361-8609    

DOI:10.1002/ajh.2830430304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA retrospective analysis was done on 43 patients with acute promyelocytic leukemia (APL) at our hospital from June 1987 to August 1992. All‐trans retinoic acid was used to induce these patients to differentiation. In the early period of induction there were risks of severe hemorrhage, which was the main cause of early death. Treatments combined with platelets and heparin or aminomethylbenzoic (PAMBA) were given to patients with abnormal coagulation. As a result only 4 out of 43 patients died of intracranial bleeding at 4–12 days when their white blood cell (WBC) counts peaked. The combination of retinoic acid (RA) and HA chemotherapy could reduce hyperleukocytosis during the RA induction course. None of 7 patients died at early stage with this treatment combination. Our studies showed that it could predict the onset of remission at early stage through observations on the successive changes of karyotypes and morphology of the bone marrow and peripheral blood cells. Our studies also showed that the growth of CFU‐F could be inhibited by RA. We think that it may play a role in the RA‐induced differentiation. In 4 years of follow‐up the overall leukemia‐free survival (LFS) was 80% with a relapse rate of 45%. Thirty‐five patients out of 43 cases were still alive in remission, and one was alive in relapse. All 11 out of 43 patients relapsed within 3 years, but the relapses occurred later, after 3 years duration of remission (P<.01). Retinoic acid failed to induce 5 patients who relapsed with the continuation treatment of RA and chemotherapy alternatively. In order to overcome the resistance to RA, the continuation treatment of simple chemotherapy had been administered following CR. Two cases achieved remission in this way. The difference of resistant events to RA reached significance between these 2 groups of different continuat

ISSN:0361-8609    

DOI:10.1002/ajh.2830430305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractEarly diagnosis is necessary for the treatment of disseminated intravascular coagulation (DIC), but criteria for the stage preceding the diagnosis of DIC (pre‐DIC) have not yet been established. To clarify hemostatic abnormalities that occur before the onset of DIC, we performed hemostatic studies in 117 patients within at least a week before the onset of DIC (pre‐DIC), in 237 patients with DIC, and in 50 patients without DIC or pre‐DIC (non‐DIC). Levels of FDP, PT, and fibrinogen, and platelet counts were significantly abnormal after the onset of DIC, but not before. Thrombin‐antithrombin III complex (TAT), plasmin‐α2 plasmin inhibitor complex (PIC), and FDP‐D‐dimer levels were significantly higher before the onset of DIC compared to the non‐DIC patients.Hemostatic abnormalities were observed within a week before the onset of DIC. Monitoring the plasma levels of TAT, PIC, and FDP‐D‐dimer might be useful for the diagnosis

ISSN:0361-8609    

DOI:10.1002/ajh.2830430306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAlthough combination chemotherapy induces complete remission in 60–90% of adults with acute lymphoblastic leukemia, only 20–45% of patients remain in continued remission 5 years from diagnosis. For patients with a short first remission, multiple relapses, or patients with disease refractory to initial induction chemotherapy, few salvage treatments are successful. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of etoposide (100 mg/m2IV qd × 5), ifosfamide (1.5 g/m2/d × 5), and mitoxantrone (8 mg/m2/d IV × 3) in 11 adult patients with relapsed or refractory ALL. The median follow‐up of all patients completing therapy is 208 days (30–484+ days). Eight of 11 (73%; 95% confidence interval 45–92%) achieved a complete remission, two patients failed to enter remission, and one patient died of multiorgan system failure shortly after receiving therapy. Median DFS is 96 days and median survival from remission is 234 days. Five patients who achieved CR subsequently relapsed with a median time to relapse of 80 days (50–151 days). Median time to granulocyte>.5 × 109/L was 28 days (21–46 days) and the median time to platelet recovery>20 × 109/L was 24 days (21–39 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. These results demonstrate that the combination of etoposide, ifosfamide, and mitoxantrone can be used as an effective salvage therapy for patient

ISSN:0361-8609    

DOI:10.1002/ajh.2830430307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractIn anemia of chronic disease (ACD) in rheumatoid arthritis (RA) a decreased iron uptake and transferrin binding by erythroblasts are postulated to play a pathophysiological role. To examine whether this is related to changes in transferrin receptor expression by erythroblasts, we studied bone marrow from 5 healthy controls, 5 nonanemic RA patients, and 9 RA patients with ACD. Bone marrow mononuclear cells were incubated with increasing concentrations of125I‐transferrin and specific binding data were analyzed by the method of Scatchard. The number of transferrin receptors on erythroblasts from RA patients with ACD was significantly lower as compared to nonanemic RA patients (P<.05) and controls (P<.02). The affinity of the transferrin receptor tended to be lower in ACD. These preliminary data may indicate that transferrin receptor expression by erythroblasts is impaired in ACD. Since the rate of erythroid iron uptake is mainly determined by the number of transferrin binding sites, this may explain a decrease in erythroblast iron availability in ACD in R

ISSN:0361-8609    

DOI:10.1002/ajh.2830430308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractMonosomy 7 (–7) is one of the most common chromosomal abnormalities found in the leukemic cells of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Because patients with –7 have a poor prognosis, their identification is important for treatment planning. Conventionally, –7 is detected by the G‐banding technique. This study examines the use of fluorescent in situ hybridization (FISH) methodology to detect –7 cells in interphase nuclei and metaphase chromosomes. Fifteen AML or MDS patients whose leukemic cells were found to have –7 by G‐banding at disease presentation were studied. In 13 of these patients, –7 could be detected in interphase by FISH using a chromosome 7‐specific centromeric DNA probe. The two patients whose leukemic cells were not detectable by interphase FISH had –7 and t(1q;7p), which were detectable by FISH in metaphase using a chromosome 7‐specific painting probe. Metaphase FISH was particularly useful in further defining chromosome 7 defects in cells that contained aberrant or marker chromosomes. For example, in 6 patients, chromosome 7 sequences were detectable in aberrant or marker chromosomes by metaphase FISH, but not by G‐banding. These results suggest that metaphase FISH is an important adjunct to conventional cytogenetic methods for defining chromosome 7 abnormalities in AML and MDS patients. Furthermore, interphase FISH is useful for follow‐up studies in patients who are found informative for the F

ISSN:0361-8609    

DOI:10.1002/ajh.2830430309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe translocation (8;21)(q22;q22) is commonly associated with acute myeloid leukemia (AML) M2 according to the French‐American‐British (FAB) classification. We describe 11 cases of t(8;21) diagnosed by strict FAB criteria. Six cases were diagnosed as AML M2, 3 cases as AML M4, 1 case as refractory anemia with excess of blasts in transformation, and 1 case as Philadelphia chromosome negative chronic myeloid leukemia in acceleration. Translocation (8;21) could thus occur in a wider variety of hematological abnormalities. Accordingly, we propose that t(8;21) may involve different hemopoietic linea

ISSN:0361-8609    

DOI:10.1002/ajh.2830430310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe assessed in vivo antimalarial action of a lipophilic iron (III) chelator belonging to a new synthetic family of biomimetic siderophores previously termed reversed siderophores (RSFs). The family member, RSF ileum2, was chosen for its high membrane permeability and fast irreversible inhibition of human malaria parasite growth in vitro. [Shanzer A, et al.,Proc Natl Acad Sci USA88:6585, 1991 and Lytton SD, et al.,Blood81:214, 1993]. The lipophilic drug was administered to Swiss mice by subcutaneous route in fractionated coconut oil at a dosage of 0.37 g/kg every 8 hr with no adverse reactions observed. After 3–4 injections demonstrable suppression ofPlasmodium vinckei petteriinfection was observed and an additional 3–4 injections resulted in 2–3‐fold lower parasitemia with prolonged survival time over sham‐injected con

ISSN:0361-8609    

DOI:10.1002/ajh.2830430311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY