Antithymocyte globulin for patients with myelodysplastic syndrome

Twenty-five transfusion-dependent myelodysplastic syndrome (MDS) patients (with < 20% blasts) were treated in a phase II study with antithymocyte globulin (ATG) at 40 mg/kg/d for four doses and then followed with blood counts every 2 weeks and clinic visits every 3 months, for a median of 14 months (range 1-38 months). 11 (44%) patients responded and became transfusion-independent after ATG, including three complete responses, six partial responses, and two minimal responses. Responses were observed in 9/14 patients (64%) with refractory anaemia (RA) and 2/6 patients (33%) with refractory anaemia with excess blasts (RAEB). Median response duration was 10 months (range 3-38 months). The Kaplan-Meier estimate of overall survival was 84% at 38 months, with one early death due to pneumonia and two deaths from disease progression to leukaemia. Side-effects consisted mainly of mild serum sickness in all patients. A single course of ATG restored haemopoiesis in some patients with MDS and was well tolerated.     

Testicular extramedullary myeloid cell tumor in a patient with myelodysplastic syndrome

We report herein a case of extramedullary myeloid tumor arising bilaterally in the testes of a 66-year-old man, who had previously been diagnosed with myelodysplastic syndrome. Light microscopy of the testicular neoplasm demonstrated a tumor composed of large, slightly polygonal cells with pale blue to weakly eosinophilic cytoplasm. The tumor cells were immunoreactive for CD45, myeloperoxidase, lysozyme, CD43, and MB2. Many of the cells also expressed chloroacetate esterase. Peripheral blood and bone marrow findings were consistent with chronic myelomonocytic leukemia (FAB-CMML), particularly in the most recent material, which showed clear cellular dysplasia and an increase in the percentage of blasts in the bone marrow (15% to 20% of all nucleated cells). This case of extramedullary myeloid tumor is unusual in view of the patient's age and the testicular location. It emphasizes the importance of including extramedullary myeloid tumor in the differential diagnosis of histologically undifferentiated large-cell tumors, as well as a need to use a broad panel of immunohistochemical stains in such cases.     

Karyotype studies of patients with a myelodysplastic syndrome]

BACKGROUND: This study examined the sources used by cancer patients to obtain helpful information regarding their treatment options and side effects and the major predictors that facilitated usage of information. METHODS: The survey was administered to a representative sample of cancer patients in Texas. The cancer treatment facilities from which the patients were sampled were part of the University of Texas M. D. Anderson Cancer Center's Texas Community Oncology Network. A total of 593 patients (65%) out of 910 contacted responded to the survey. RESULTS: The patients reported that providers such as physicians and nurses were the most helpful sources of information. White patients tended to use books and reference materials more heavily to gather additional information regarding their treatment, while black patients relied on pamphlets and television. Educational level appeared to have a major influence on the black patient's use of printed materials. CONCLUSIONS: The results document the important role that providers play in influencing patients' treatment decisions. Effective ways to communicate with cancer patients are different for patients with different racial backgrounds. Implications for the future development of patient education materials and cancer prevention initiatives targeting ethnic minorities are addressed.     

HAG预激化疗作为诱导缓解方案治疗老年人急性髓系白血病和骨髓增生异常综合征的临床观察

目的 观察HAG预激化疗作为诱导缓解方案在治疗老年急性髓系白血病(AML)和骨髓增生异常综合征-难治性贫血伴原始细胞增多型(MDS-RAEB)患者中的疗效.方法 对应用HAG预激方案治疗的21例AML和9例MDS-RAEB患者(≥60岁)的临床资料进行回顾性总结,包括疾病完全缓解(CR)率、有效率以及不良反应.结果 21例老年AML患者中,HAG诱导缓解的有效率为66.7%(14/21),其中CR率为47.6%(10/21);9例老年MDS-RAEB患者中,CR率为55.6%(5/9):HAG预激化疗的主要不良反应为因骨髓抑制继发的感染,调整化疗方案后所有患者均能耐受.结论 HAG预激化疗作为诱导缓解方案适用于老年AML和MDS-RAEB患者.     

骨髓增生异常综合征T淋巴细胞异常与克隆造血

目的 了解T淋巴细胞异常在骨髓增生异常综合征(MDS)克隆造血中的作用.方法 对76例MDS患者的染色体核型、T淋巴细胞亚群及激活状态进行分析.结果 正常核型36例,异常核型40例,异常发生率52.6%.40例异常核型中,三体8(+8)24例,占异常核型的60.0%.与健康对照组比较,MDS患者CD+3 CD-19、CD+3 CD-4 CD+8以及CD+3 HLA-DR+细胞百分率显著升高,CD-3(CD16 CD56)+细胞的百分率明显降低.将MDS患者进行核型分组,异常核型组CD+3(CD16 CD56)+细胞的百分率显著高于正常对照组.将+8核型从MDS异常核型中独立出来进行分析,CD+3 CD+4 CD-8细胞的百分率明显低于正常核型以及其他异常组,CD4/CD8的比值明显低于健康对照组.结论 MDS存在T淋巴细胞异常,异常核型MDS可能恶性克隆增殖更为优势,预后更差.+8核型MDS存在更为严重的免疫监视功能下降,导致恶性克隆过度增殖与残存造血过度受抑.     

Multiple myeloma developing myelodysplastic syndrome with thrombocytosis

A 64-year-old woman with multiple myeloma, IgG lambda type Durie-Salmon Stage II, was admitted because of gradually developing anemia and increased blasts with abnormal karyotype in her bone marrow after 10 years of treatment. The chromosomal analysis showed 44, XX, del(5q), del(7q), -9, add(12p), -21, typical of secondary MDS due to the cumulative alkylating agents. Thrombocytosis concomitantly occurred with emergence of chromosomal abnormality, but the serum interleukin 6 level was not elevated, which suggested that it was related to development of secondary MDS.     

Measurement of secondary colony formation after 5 weeks in long-term cultures in patients with myelodysplastic syndrome

Pancytopenia is a frequent manifestation of myelodysplastic syndromes (MDS). In the presence of an empty bone marrow, clinical distinction from aplastic anemia may be difficult. The hypoplastic marrow morphology seen in some cases of MDS raises questions about etiologic and pathophysiologic relationships between aplastic anemia and MDS. The goal of our study was to compare the degree of the hematopoietic failure in these diseases at the level of the most immature progenitor and stem cells that can be measured in vitro. In a systemic, prospective fashion, we have studied bone marrow (n = 45) and peripheral blood (n = 33) of patients with MDS for the number of long-term culture initiating cells (LTC-IC) in comparison to 17 normal controls and patients with new, untreated aplastic anemia (46 marrow; 62 blood samples). Due to the low numbers of cells available for the analysis, formal limiting dilution analysis could not be performed, instead secondary colony-forming cells (CFC) after 5 weeks of LTBMC were measured. As the number of these cells is proportional to the input number of LTC-IC, the number of secondary CFC per 10(6) mononuclear cells (MNC) initiating the LTBMC can be used as a measure of the content of immature stem cells in bone marrow and peripheral blood. The MDS group consisted of 34 RA, three RARS, eight RAEB and two RAEB-T patients with mean absolute neutrophil values of 1992, 1413, 1441, and 380 per mm3, respectively. The diagnosis was established based on bone marrow morphology and results of cytogenetic studies. In comparison to controls (147 +/- 38/10(6) MNC), significantly decreased numbers of bone marrow secondary CFC were found in MDS: in patients with RA and RARS, 21 +/- 7 secondary CFC per 10(6) bone marrow MNC (P < 0.001); patients with RAEB and RAEB-T: 39 +/- 12 CFC per 10(6) marrow MNC (P < 0.001). In all groups tested, the decrease in peripheral blood secondary CFC numbers was consistently less pronounced. In MDS patients with hypocellular bone marrow, secondary CFC were lower but not significantly different in comparison to MDS with hypercellular marrow (18 +/- 6 vs 35 +/- 11; NS; hypoplastic bone marrow also was not associated with significantly lower neutrophil counts). However, in 24% of patients with MDS, bone marrow secondary CFC were within the normal range, while in the aplastic anemia group only one of the patients showed secondary CFC number within normal range. Bone marrow and blood secondary CFC numbers in hypoplastic RA were significantly higher than those in severe aplastic anemia 919 +/- 5 in bone marrow, P < 0.01; 7 +/- 2 in blood, P < 0.05). This trend was even more pronounced in hypoplastic RA with chromosomal abnormalities. However, no significant differences were found between the secondary CFC numbers in hypoplastic RA and moderate aplastic anemia. We concluded that, although the deficiency in the stem cell compartment is less severe in MDS than in aplastic anemia, depletion of early hematopoietic cells is an essential part of the pathophysiology in both diseases.     

Full chemotherapy in elderly patients with small cell bronchial carcinoma

The changing distributions of collagens and glycosaminoglycans have been studied at the attachments of the medial collateral ligament during postnatal development. The ligament is of particular interest because it has a fibrocartilaginous attachment to the femoral epiphysis, but a fibrous one to the tibial metaphysis. Ligaments were examined in rats killed at birth and at 2, 4, 6, 8, 10, 20, 30, 45, 60, 90 and 120 days after birth. Cryosections were immunolabelled with monoclonal and polyclonal antibodies against types I and II collagen, chondroitin 4 and 6 sulfate, dermatan and keratan sulfate. Although the ligament is attached at both ends to bones that develop from cartilage, there was a striking difference in collagen labelling. Type II collagen was only found in spicules of calcified cartilage in bone beneath the tibial enthesis after ossification had commenced, but there was a continuous band of labelling at all stages of development at the femoral enthesis. Initially, the cartilage at the femoral attachment lacked type I collagen, but by 45 days labelling was continuous from ligament to bone. Continuity of labelling was seen much earlier at the tibial enthesis, as soon as bone had formed. There were also marked changes in glycosaminoglycan distribution. Keratan sulfate was present at both entheses up to 45 days, but only at the femoral enthesis thereafter. Both attachments labelled throughout life for dermatan sulfate, but chondroitin 4 and 6 sulfate were only found at the femoral end. The results suggest that enthesial cartilage at the femoral attachment was initially derived from the cartilaginous bone rudiment but was quickly eroded on its deep surface by endochondral ossification as bone formed at the attachment site. It was replaced by fibrocartilage developing in the ligament. This mechanism allows enthesis cartilage/fibrocartilage to contribute to the growth of a bone at a secondary centre of ossification in addition to dissipating stress at the ligament-bone junction.     

Reversible malabsorption of folic acid in the elderly with nutritional folate deficiency

The question of the point of impact of the electric current in the galvanic vestibular test is not solved. An important feature is that, after destruction of both the vestibular end organs, a galvanic nystagmus can still be provoked. The effect of a direct current on the spontaneous nystagmus following partial or total destruction of the vestibular end organs was investigated. The frequency of the spontaneous nystagmus diminishes when the electric stimulus causes an eye movement in the same direction as the fast phase of the nystagmus, the frequency increases when the polarity of the electric stimulation is reversed. Simultaneous application of torsion-swing and electric stimulation causes a summation of the separate effects. Our findings confirm the conculsions drawn by Ledoux (4, 5) from his findings in frogs.     

Red blood cell glutathione status in patients with gastrointestinal malignancies treated with 5-fluorouracil

As an alternative to surgical splenectomy, partial splenic embolization was performed in seven children for hypersplenism manifested by splenomegaly, thrombocytopenia, leukopenia, and erythrocyte hemolysis. Within a few days, platelet and leukocyte counts rose significantly in all patients and were maintained in six of seven patients during a follow-up period of 9 to 69 months. Spleen size and abdominal distention also decreased significantly in all children. There were no infectious complications.     

Lymphoblastic transformation of myelodysplastic syndrome

Mielodysplastic syndromes (MDS) are clonal disorders of the hemopoietic stem cell. About one third of the cases terminate in an acute leukemia, usually acute myeloblastic leukemia. However, few cases of transformation into acute lymphoblastic leukemia (ALL) have been described. We present a case of refractory anemia that transformed into ALL two months after diagnosis and was successfully treated with conventional chemotherapy. Two years later a hyperfibrotic form of MDS was detected in the patient, that soon after terminated in acute megakaryoblastic leukemia. The course of MDS in the present case provides evidence that MDS can involve a pluripotent stem cell, presenting clonal evolution, documented by successive changes in its clinical and hematological features.     

Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes

Among acquired stem cell disorders, pathological links between myelodysplastic syndromes (MDS) and aplastic anaemia (AA), and paroxysmal nocturnal haemoglobinuria (PNH) and AA, have been often described, whereas the relationship between MDS and PNH is still unclear. We analysed blood cells of patients with MDS to determine the incidence of the PNH clone, and analysed the PIG-A gene to find mutations characteristic of the PNH clone in MDS. In four (10%) of 40 patients with MDS, flow cytometry showed affected erythrocytes and granulocytes negative for decay-accelerating factor (DAF) and CD59. The population of affected erythrocytes was smaller in MDS patients with PNH clone (MDS/PNH) than in patients with de novo PNH, and haemolysis was milder in the MDS/PNH patients. PIG-A mutations were found in granulocytes of all patients with MDS/PNH. In type and site, the PIG-A mutations were heterogeneous, similar to that observed in de novo PNH; i.e. no mutation specific to MDS/PNH was identified. Of note, three of four patients with MDS/PNH each had two PNH clones with different PIG-A mutations, suggesting that PIG-A is mutable in patients with MDS/PNH. In a MDS/PNH patient with trisomy 8, FISH detected a distinct karyotype in a portion of granulocytes with PNH phenotype, indicating that PNH and MDS partly shared affected cells. Thus, MDS predisposes to PNH by creating conditions favourable to the genesis of PNH clone. Considering the increasing prevalence and incidence of MDS, these disorders could be useful for investigating the mechanism by which PIG-A mutation is induced.     

Relationship between autoantibody and dermatosis in myelodysplastic syndrome

We analyzed the relationship between autoantibody and dermatosis in 22 patients with myelodysplastic syndrome (MDS). These MDS patients consisted of five cases with refractory anemia (RA), three RA with ringed sideroblasts (RARS), eight RA with excess of blasts (RAEB), four RAEB in transformation (RAEB-t), and two chronic myelomonocytic leukemia (CMMoL) according to the FAB classification of MDS. The autoantibody was detected in seven patients, of whom four had rheumatoid factor (RF) and three had antinuclear antibody (ANA). Neither RF-positive nor ANA-positive MDS patients had other autoantibodies. Dermatosis was observed in nine cases of these 22 MDS patients. Five of 7 MDS patients (71%) with autoantibody developed dermatosis in their clinical course, as did four of 15 MDS patients (27%) without autoantibody. All four MDS patients with RF had dermatosis such as anaphylactoid purpura, xerotic dermatitis, thrombophlebitis, ephelides, and genital herpes. One of three MDS patients with ANA had pruritus senilis. The four MDS patients without autoantibody had dermatosis such as erythema nodosum, ichthyosis vulgaris, Sweet syndrome, and thrombophlebitis. Three of four MDS patients with RF had normal liver function tests, while three MDS patients with ANA showed liver dysfunction. Our studies presented here suggested that the dermatosis could develop frequently in MDS patients with autoantibody and that RF was closely related to development of dermatosis in MDS patients, although the dermatosis is not specially fixed.     

Chronic parvovirus infection mimicking myelodysplastic syndrome in a child with subclinical immunodeficiency

1. The effect of cyclo(D-Trp-D-Asp-Pro-D-Val-Leu) (or BQ123), a selective ETA receptor antagonist, on the vasoconstrictor and diuretic responses elicited by endothelin-1 (ET-1) was examined in conscious sheep with chronic indwelling renal arterial cannulae. 2. Using low dose close renal arterial infusion, ET-1 has potent effects on the kidney causing a marked decrease in effective renal plasma flow and an increase in urine output and free water clearance in the normally hydrated animal. 3. The vasoconstrictor response to renal arterial infusion of ET-1 at 5 micrograms/h was blunted by renal arterial infusion of the ETA receptor selective antagonist, BQ123 (400 micrograms/h). 4. In contrast, the effect of ET-1 on urine production and free water clearance was not affected by this dose of BQ123. 5. The differential effect of BQ123 on renal blood flow and urine production suggests that these effects of endothelin on the kidney are mediated through different receptor mechanisms.     

Response to recombinant human erythropoietin in patients with myelodysplastic syndromes

OBJECTIVES: The impact of a positive surgical margin in otherwise confined prostate cancer after radical prostatectomy remains unclear. We analyzed the outcome of a large number of patients with organ-confined prostate cancer according to the presence and anatomic site of margin positivity. METHODS: We evaluated 2712 prostatectomy patients with Stage pT2N0 cancer (ie, no evidence of extra-prostatic disease, seminal vesicle or regional node involvement) and no prior therapy who were treated by radical prostatectomy between 1987 and 1995 at Mayo Clinic. A total of 697 patients (26%) had positive margins. To assess the effect of margin status in the absence of treatment, 378 patients with postoperative adjuvant therapy were not considered for the study group: the final group consisted of 2334 patients. RESULTS: Overall, 253 (58%) tumors were positive at the apex and/or urethra, 85 (19%) at the prostate base, 11 (2.5%) at the anterior prostate, and 174 (40%) at the posterior prostate; 89 (20%) had at least two margins involved and 21 (8.3%) had more than two involved. The apex/urethra was the only positive anatomic site in 183 (42%). Five-year survival free of clinical recurrence or prostate-specific antigen (PSA) biochemical failure (postoperative serum PSA of 0.2 ng/mL or more) for patients with a single positive margin was 79% for apex or urethra, 78% for anterior/posterior, and 56% for prostate base. Five-year survival free of clinical recurrence or PSA (biochemical) failure was slightly higher for those with one versus two margin-positive regions (77% versus 68%, respectively). Multivariate analysis revealed that positive surgical margins were a significant predictor of clinical recurrence and PSA (biochemical) failure (relative risk [95% confidence interval]: 1.65 [1.24, 2.18]) after controlling for Gleason grade, preoperative PSA, and deoxyribonucleic acid (DNA) ploidy. The effect of margin positivity on recurrence at a specific anatomic site (versus negative margins or positive at a different anatomic site) revealed the prostate base to be the only significant anatomic site when adjusted for grade, PSA, and ploidy. Five-year survival free of the combined clinical or PSA failure end point for those with versus those without positive margins at the prostate base was 56% versus 85%, respectively (P < 0.0001). CONCLUSIONS: Positive surgical margins are a significant predictor of recurrence in Stage pT2N0 cancer, which is independent of grade, PSA, and DNA ploidy. The impact of positive margin status on recurrence-free survival appears to be anatomic and site-specific, with prostate base positivity significantly associated with poor outcome. The benefit of adjuvant therapy based on anatomic site-specific margin positivity remains to be tested in order to optimize recurrence-free survival.     

A study comparing VVI and DDI pacing in elderly patients with carotid sinus syndrome

Display on the yeast cell wall is well suited for engineering mammalian cell-surface and secreted proteins (e.g., antibodies, receptors, cytokines) that require endoplasmic reticulum-specific post-translational processing for efficient folding and activity. C-terminal fusion to the Aga2p mating adhesion receptor of Saccharomyces cerevisiae has been used for the selection of scFv antibody fragments with threefold decreased antigen dissociation rate from a randomly mutated library. A eukaryotic host should alleviate expression biases present in bacterially propagated combinatorial libraries. Quantitative flow cytometric analysis enables fine discrimination of kinetic parameters for protein binding to soluble ligands.     

Plasma soluble interleukin-2 receptors in patients with myelodysplastic syndromes

We examined the plasma soluble interleukin-2 receptor (sIL-2R) level in 80 subjects with myelodysplastic syndromes (MDS) and analyzed its correlation with hematologic/immunologic parameters and the subsequent clinical course. Compared with low-risk MDS (refractory anemia (RA) and RA with ringed sideroblasts) and normal individuals, the plasma sIL-2R level was significantly elevated in high-risk MDS (three other MDS subtypes and acute leukemia following MDS) patients. There was a significant negative correlation between the plasma sIL-2R level and the absolute counts of T and natural killer cells. Furthermore, the plasma sIL-2R level showed a significant positive correlation with the total cell mass and blast mass in particular, in the marrow, but not with the absolute count of IL-2Ralpha-chain-positive lymphocytes in the circulation. Fourteen of our 40 low-risk MDS subjects developed at least one of the following events during the follow-up period: erythrocyte transfusion dependence, infections requiring hospitalization, disease progression or MDS-related death. The plasma sIL-2R level was significantly higher in these patients than in event-free low-risk cases. By logistic regression analysis of various parameters in the 40 low-risk subjects, the plasma sIL-2R level was identified as a valuable independent parameter for predicting the development of events. Based on these findings, we hypothesize that the sIL-2R plays a role in the development of morbidity and mortality in MDS by inducing immunologic dysfunction.