Sotos Raptis

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): treatment outcome, relapses, prognostic factors. A single-center experience of 48 cases.

Abstract The thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is a rare disorder characterized by microangiopathic hemolysis and thrombocytopenia. We have undertaken a retrospective analysis of the clinical characteristics, treatment outcome, and prognosis of 48 patients diagnosed and treated in our institution during a 13-year period. Among our patients 22 (46%) had fever, 35 (73%) neurological abnormalities, and 22 (46%) renal impairment at presentation of the syndrome. All patients were treated with a multimodality regimen including plasma exchange, steroids, antiplatelet agents, and IgG infusion. Of the 48 patients, 41 achieved complete remission, two had a partial response, and five had no response and died of progressive disease. Within a median follow-up period of 40 months, ten of the 41 patients who had achieved remission relapsed, most of them within the first 2 years, and nine of these responded promptly to plasma exchange therapy. Eight deaths were observed, seven of refractory disease and one in fourth relapse. The analysis of prognostic factors revealed advanced age and severe renal impairment (creatinine levels above 2 mg%) as the only parameters associated with treatment failure and poor outcome. However, none of the pretreatment characteristics proved to be of prognostic value regarding the probability of relapse. In conclusion, TTP/HUS represent a syndrome of variable clinical expression and aggressiveness. The use of a multimodality regimen in our series produced a high response rate. Nevertheless, the early identification, based on clinical characteristics, of poor-prognosis cases that probably need more or alternative forms of treatment is an issue that remains to be elucidated in prospective trials.

Myelodysplastic syndromes: Analysis of 131 cases according to the FAB classification

The clinical and haematological findings in 131 patients with myelodysplastic syndromes (MDS), none of which had previously received chemotherapy or radiotherapy, classified according to the FAB criteria, were analysed. The distribution among the 5 subgroups was: RA 31 patients, RAS 19, RAEB 23, CMML 29 and RAEBT 29 patients. There were difficulties in the classification of 24 patients. These included, first, 8 cases with myeloid hyperplasia of the bone marrow (BM) but without mono‐cytosis or excess of blasts of the BM. They were classified as RA. Second, 8 cases with sideroblastosis but with monocytosis or excess of blasts of the BM were classified 3 as RAEB, 2 as CMML and 3 as RAEBT. Finally, 8 cases with absolute monocytosis and BM blasts 15–30% were classified as CMML. 37 of 82 dead patients (45.1%) had transformed to acute non‐lymphoblastic leukaemia (ANLL). The incidence of evolution to ANLL was low for RA and RAS (6.30% and 12.5% respectively), while it was 37.5% for RAEB, 57.1% for CMML and 77.2% for RAEBT. The median survival for each subgroup was: RA 18 months; RAS 25; RAEB 13; CMML 14 and RAEBT 10 months. It is concluded that the FAB classification with some modifications recognises group of MDS with different prognosis.

Primary extranodal non-Hodgkin's lymphoma of the head and neck

Primary extranodal NHL of the head and neck (HN-NHL) accounts for 10-20% of all cases of NHL. Despite their frequency, the natural history and biological behaviour of these lymphomas is poorly understood. In this study we analysed the data 116 cases of HN-NHL. There were 65 males and 51 females with a median age of 56 years. The distribution among different anatomical sites was: tonsils 56 cases (48.3%), nasopharynx 15 (12.9%), mandible/gingiva 9 (7.8%), hard palate 7 (6%), parotis 6 (5.2%), nasal cavity 6 (5.2%), hypopharynx/larynx 6 (5.2%), thyroid 5 (4.3%), ocular adnexa 4 (3.5%), paranasal sinuses 2 (1.7%). The patients were treated with radiotherapy alone (14 cases), combined chemotherapy (52 cases) and combined modality (50 cases). According to the WF histological classification 73 cases (62.9%) had intermediate, 32 (27.6%) high and 11 (9.5%) low grade. Patients were separated in two groups: Tonsillar NHL (56 cases) and NHL of all other sites (non-tonsillar group-60 cases). A comparison between the two groups showed that there was no statistically significant difference with respect to age, sex, and histological subtypes. Also treatment response was similar (82.1% for the tonsillar vs 83.3% for the non-tonsillar). The two groups differed in stage distribution, survival and pattern of relapse. Stage I was more frequent in the non-tonsillar NHL (60%) in contrast to tonsillar NHL where stage II was more prominent (51.8%). Median survival was 86 months for the tonsillar while it has not been reached yet for the non-tonsillar patients. Patients in stage I and stage II of the non-tonsillar group had better survival compared to stages I and II of the tonsillar patients. Finally GI tract was a common site of relapse in the tonsillar group while a considerable number in CNS relapses were observed in the non-tonsillar group. We concluded that HN-NHL constitutes a heterogeneous group of patients. Tonsillar lymphomas represent a distinct group with some special clinicopathological findings.

Massive hemothorax due to intrathoracic extramedullary hematopoiesis in a patient with hereditary spherocytosis

Abstract Extramedullary hematopoiesis (EMH) is a rare disorder, characterized by the appearance of hematopoietic elements outside of the bone marrow, which occurs in patients with chronic myeloproliferative disorders or congenital hemolytic anemias. We report on a 64-year-old man with hereditary spherocytosis, who presented with anemia, jaundice, intrathoracic EMH, and massive hemothorax. The diagnosis of EMH was established after computer tomography (CT)-guided punctuation of the paravertebral mass. The patient underwent splenectomy and thoracic drainage. After 1 year, the patient is in good health, with normal hemoglobin values, and hemothorax has not recurred.

Changes in serum lipids and lipoproteins in cancer patients during chemotherapy.

SummaryWe studied serum lipid and lipoprotein changes occurring during chemotherapy in 57 patients with chemosensitive cancers, including 18 malignant lymphomas, 18 breast carcinomas, 14 small-cell lung carcinomas, and 7 urothelial-cell carcinomas. Patients who responded favorably to chemotherapy demonstrated a significant increase in serum total cholesterol and LDL cholesterol values, with the singular exception of breastcancer patients, who exhibited a nonsignificant decrease in both of these parameters. Serum levels of free cholesterol and HDL cholesterol did not show any significant changes. Finally, serum triglycerides tended to increase after effective chemotherapy, but this was of statistical significance only in breast-cancer patients. Although our findings were based on a rather small number of patients, they indicate that the lipid and lipoprotein disorders reported in cancer patients are reversible by effective treatment of the tumor, suggesting that these disorders are a secondary phenomenon of malignancy.

Efficacy of Intravenous Immunoglobulin in the Treatment of Thrombotic Thrombocytopaenic Purpura

Thrombotic thrombocytopaenic purpura (TTP) is characterised by platelet aggregation in the capillaries, thrombocytopaenia and microangiopathic haemolytic anaemia that result in organ ischaemia, mainly of the CNS and kidneys. Since the institution of plasma exchange therapy no further treatments have been proved to improve the survival and the relapse rate of TTP patients. In this retrospective study, we evaluated the efficacy of normal human immunoglobulin treatment in 44 patients suffering from TTP. Patients were divided into two groups that either did not receive (group A: 15 patients) or received (group B: 29 patients) 400 mg/kg of human normal immunoglobulin intravenously (ivIgG) for 5 days. All patients received treatment with corticosteroids, anti-platelet agents and plasma exchange. The results clearly showed that there was no statistically significant difference between the two groups in either remission rate or time to relapse following remission. In conclusion, this study did not prove any beneficial effect of ivIgG in the treatment of TTP patients.

δ-Aminolaevulinic acid dehydratase as an index of lead toxicity. Time for a reappraisal?

Abstract. δ‐Aminolaevulinic acid dehydratase activity is traditionally accepted as the most sensitive measurable biological index of lead toxicity. We have measured δ‐aminolaevulinic acid dehydratase activity and blood lead concentration in 47 healthy controls (A), 42 iron deficient patients (B) and 38 occupationally exposed to lead subjects (C). Blood lead levels [x (SD)] did not differ between groups A and B [0.51 (0.21) and 0.43 (019) μmol L‐1, respectively] while those of group C [2.28 (0.56) μmol L‐1 were significantly higher (P < 0.001) as compared to the controls. δ‐Aminolae‐vulinic acid dehydratase activity [x (SD)] was significantly increased [3599 (1909) μmol L‐1 h‐1] in group B and decreased in group C [1052 (532) μmol L‐1 h‐1] as compared to the controls [2034 (446) μmol L‐1 h‐1] (P < 0.001). There was a significantly negative correlation of logarithm of δ‐aminolaevulinic acid dehydratase with lead in both groups B (P < 0.05) and C (P < 0.001) but not in group A (P= 0.1). δ‐Amino‐laevulinic acid dehydratase activity had a high specificity (100%) but a low sensitivity (37%) as an index of toxic lead exposure. According to our data the value of δ‐aminolaevulinic acid dehydratase measurement in the diagnosis of lead intoxication is doubtful in cases with low blood lead levels, while in the presence of iron deficiency its reliability is further reduced, since low blood lead levels may be falsely predicted. δ‐Amino‐laevulinic acid dehydratase activity should be restricted only to monitoring cases with moderate or severe lead poisoning.

Plasma lipid and lipoprotein response to carbohydrate feeding in cirrhotic patients

Serum lipids and lipoproteins, and glucose and insulin, were measured after an overnight fast, and during 3 days of a eucaloric diet rich in carbohydrate, in 15 patients with cirrhosis and seven normal subjects. Following the high-carbohydrate diet triglyceride rose in all groups but the increase in cirrhotics was lower than in normals. In normals and in cirrhotics with good liver function most of the triglyceride increment was carried in VLDL; in cirrhotics with poor liver function only 31% of the increment was found in VLDL, and 56% in triglyceride-rich LDL. In an earlier study on fat feeding, our cirrhotic patients with poor liver function had an impaired chylomicron and VLDL response; they also carried most of the triglyceride increment in triglyceride-rich LDL. The markedly impaired response of triglyceride-rich lipoproteins to both carbohydrate and fat feeding suggests that sick cirrhotics may have a problem with storage of dietary energy and that this contributes to loss of their adipose tissue.

Plasma Secretin, Pancreozymin, and Somatostatin-like Hormone in Chronic Renal Failure Patients

Twenty patients with chronic renal failure (CRF) and ten patients on hemodialysis were included in the study of plasma secretin and pancreozymin measurement. Plasma somatostatin-like hormone (SLH) was measured in seven patients with CRF, eight patients in continuous ambulatory peritoneal dialysis (CAPD), and ten patients on hemodialysis. Normal subjects were used as sex- and age-matched healthy controls. Plasma secretin, pancreozymin, and SLH were determined by radioimmunoassay. Basal plasma concentration of secretin and pancreozymin was found significantly increased in hemodialysis patients in comparison to controls. Also test meal induced a significant increase of both hormones in hemodialysis patients. Basal plasma SLH was found significantly increased in both predialysis and dialysis (hemodialysis, CAPD) patients in comparison to controls. Correlation between clinical gastrointestinal disturbances and elevated hormone levels was not found. We believe that more reliable plasma measurement of these hormones will help the clinical investigation of gastrointestinal pathophysiology in uremia for the future.

Spontaneous remission in myelodysplastic syndrome.

Abstract A 73-year-old man was admitted for investigation of pancytopenia. His physical examination was unremarkable and the bone marrow aspirate was compatible with myelodysplastic syndrome (RAEB). Cytogenetic analysis of the bone marrow revealed a trisomy 21. The patient received transfusions of packed red cells, and his condition remained stable for the next 7 months. He was then admitted with a chest infection and was treated with broad-spectrum antibiotics with satisfactory response. During his hospitalization there was a gradual increase in his complete blood count values, which persisted, resulting in a normal peripheral blood after 3 months. A bone marrow aspirate performed at that time revealed normal findings with no karyotypic abnormalities, indicating a spontaneous remission. The patient remained stable for the next 6 months; then he recurred with 20% blasts in his bone marrow and reappearance of trisomy 21in 42% of the metaphases examined. Several hematologic malignancies with spontaneous remissions have been described to date, but they have generally been short and recurrence is the rule, as in the case described. The role of endogenous cytokines in triggering these spontaneous remissions is under question, as the exact mechanism is unknown.