A predictive model for life-threatening neutropenia and febrile neutropenia after the first course of CHOP chemotherapy in patients with aggressive non-Hodgkin's lymphoma.

The purpose of this study was to develop a model for predicting the occurrence of life-threatening neutropenia (LN, ANC < or = 0.5 x 10(9)/l) and febrile neutropenia (FN, an ANC < 0.5x10(9)/l in association with a body temperature of > or = 38.3 degrees C) after the first cycle of CHOP therapy in patients newly diagnosed with aggressive NHL. One hundred and forty-five patients, aged > or = 15 years, with newly diagnosed diffuse mixed, diffuse large-cell or large-cell immunoblastic lymphoma (IWF categories, F, G, H), who had been treated with CHOP at King Chulalongkorn Memorial Hospital between June 1994 and December 1998, were entered into the study. The criteria for eligibility included complete work-up for baseline evaluation, treatment with standard CHOP chemotherapy, at least one complete blood count performed during days 8-14 post-treatment or if at any time the patients experienced a BT of > or = 38.3 degrees C and were not treated with any colony-stimulating factors (CSFs). The median age of the patients was 47 years (range, 17-78). Forty-eight percent of the patients were in stage III/IV, 36% had ECOG performance status (PS) II-IV, 30% had > or = 2 extranodal diseases, 59% had serum LDH > 1 x normal and 23% had bone marrow involvement. The frequencies of patients in the low-, low-intermediate, high-intermediate and high risk groups according to the international index were 29%, 28%, 17% and 26%, respectively. Thirty-nine percent of the patients had LN at nadir and 33% developed FN after the first course of CHOP. By using stepwise logistic regression analysis, the pretreatment variables independently predictive of the LN at nadir and the FN were serum albumin concentration of < or = 3.5 g/dl, serum LDH > 1 x normal and whether there was bone marrow involvement of lymphoma at presentation. The model, based on the incorporation of these three factors, identified three risk groups of patients with a predicted probability of developing LN at nadir of 81.5% (95% CI, 68.5-90.7) (high risk), 23.9% (95% CI, 12.6-38.8) (intermediate risk) and 4.4% (95% CI, 0.5-15.1) (low risk). The predicted rate of FN in the three groups were 72.2% (95% CI, 58.4-83.5), 17.4% (95% CI, 7.8-31.4) and 2.2% (95% CI, 0.05-11.8), respectively. In conclusion, our model could be used as a means to identify patients with newly diagnosed aggressive NHL, treated with CHOP, who are at high risk (> or = 50% probability) of developing post-first course LN and FN, in whom CSF and/or antibiotic prophylaxis might be indicated.

CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.

The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL.

Quality of life in Thai patients after bone marrow and peripheral blood stem cell transplantation: a comparison study with patients treated with conventional chemotherapy.

This study of adult patients of Thai cultural background compared the quality of life (QOL) of patients undergoing bone marrow and peripheral blood stem cell transplantation (BMT/PBSCT) with that of patients treated with conventional chemotherapy (CT). The study population comprised 59 patients who were transplant recipients (29 allogeneic, 29 autograft, and one syngeneic BMT/PBSCT) and 24 patients treated with CT for various hematologic malignancies. The participants completed a 50-item structured QOL questionnaire sent by mail. No significant differences were found between the two patient groups regarding their psychological, social, and treatment-related well-being or their overall QOL; all scores were above 75% of the total. The mean score regarding the physical domain, however, was significantly lower in BMT/PBSCT patients. Areas of highest concern in both groups were sexuality and financial burden. Happiness, functional ability, financial burden, and the degree of familial acceptance were the most important predictors of the self-rated QOL in BMT/PBSCT patients. Seventy-five percent of BMT/PBSCT patients would be willing to undergo the procedure again under the same circumstances. These results indicated that the QOL of Thai patients undergoing BMT/PBSCT was in general satisfactory and comparable to patients treated with conventional CT.

The effects of green pit viper (Trimeresurus albolabris and Trimeresurus macrops) venom on the fibrinolytic system in human.

Green pit viper (Trimeresurus albolabris and Trimeresurus macrops) venom was found to have a thrombin-like effect in vitro but cause a defibrination syndrome in vivo. The effects of venom on fibrinolytic system have not been well characterized. This knowledge can help to define the roles of antifibrinolytic therapy, give insights in fibrinolytic system regulation and potentially lead to identification of a new profibrinolytic agent from this venom. Forty-six cases of green pit viper bites were studied for various coagulation and fibrinolytic parameters and correlated with serum venom levels measured by ELISA. Fibrinolytic system activation is very common as indicated by low plasminogen (50%), low antiplasmin (56.5%) and elevated fibrin-fibrinogen degradation products (FDPs, 97.4%) levels. FDP test is very sensitive and a normal level is useful for exclusion of systemic envenomation. In contrast to some other models of defibrination syndrome, such as Russell viper (Daboia russelli siamensis), elevation of plasminogen activator activity (PA) was found indicating a hyperfibrinolytic state. Definite increase in tissue-type plasminogen activator (t-PA) antigen (p = 0.00075) with a modest elevation of its inhibitor plasminogen activator inhibitor-1 (PAI-1) (p = 0.27) probably contributes to this effect. This supports the idea that the balance between plasminogen activators and inhibitors can determine fibrinolytic responses in pathologic states. Fibrinopeptide A levels were markedly elevated (68.43 +/- 51.57 ng/ml in cases and 2.83 +/- 3.80 ng/ml in control, p < 0.0001) and correlated well with clinical severity suggesting that the fibrin deposition from the thrombin-like effect is the main mechanism of fibrinolysis. Therefore, antifibrinolytic agents probably have no role in treatment. However, the components of green pit viper venom that have these profibrinolytic effects in human are interesting and should be further identified.

Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical analysis of 117 cases.

To gain more insight into the understanding of myelodysplastic syndromes (MDS) as they occur in Thailand, a retrospective clinicopathologic analysis was conducted in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996 at the five major medical centers in various geographic regions of the country. The central reviewers independently examined the bone marrow and peripheral blood smears of all the patients and classify the disease according to the French-British-American (FAB) classification. There were a total of 117 eligible patients. The median age of the patients was 56 years (range 16-86). The male:female ratio was 1:1. Thirty-two percent of the patients were younger than 40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML, 9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of the patients. In the 34 patients in whom the cytogenetics in the bone marrow were analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were the most common aberration, each being detected in 26.7% of the patients. Transfusions were the main therapeutic modality in 80% of the patients. Kaplan-Meier analysis revealed a 5 year survival rate of 29% for the whole group with a median survival of 24 months. Twenty-five percent of the patients had progressed to acute myelogenous leukemia (AML) with a median time to disease-progression of 23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4, 19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression analysis revealed the percentage of blasts in the bone marrow as the only parameter significantly associated with survival and disease progression. On comparison with data from other countries, the age of Thai patients with MDS is considerably lower than the western population but is comparable to other asian countries. The distribution of the FAB subtypes and the survival of the patients are similar. The major prognostic features, however, lie in the percentage of blasts in the bone marrow rather than the degree of the observed cytopenia.

The role of serum ferritin in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis.

OBJECTIVES: To determine the diagnostic values of serum ferritin and other conventional laboratory tests in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis. DESIGN: Cross-sectional study for diagnostic tests. SETTING: University hospital. SUBJECTS: Seventy-two consecutive patients with liver cirrhosis in whom the haemoglobin level was less than 13.0 g dL(-1) for men and 12.0 g dL(-1) for women. The diagnosis of liver cirrhosis was based on characteristic clinical and hepatic ultrasonographic findings. MAIN OUTCOME MEASURES: By using absence of bone marrow iron as the standard criterion, the diagnostic powers of mean corpuscular volume, transferrin saturation, serum ferritin and the presence of hypochromic red cells in the diagnosis of iron deficiency were compared by analysing the likelihood ratios, the area under the receiver operating curves (ROC) and the stepwise logistic regression associated with each test. RESULTS: Twenty-nine patients (40.3%) demonstrated no stainable iron in the bone marrow. The likelihood ratios, the area under the ROC and the stepwise logistic regression indicated that serum ferritin was the most powerful test predictive of iron deficiency. Other tests added little further diagnostic values. The likelihood ratios associated with the serum ferritin levels were as follows: <50 microg L(-1), 22.3; 51-200 microg L(-1), 1.5-1.8; 201-400 microg L(-1), 1.0; >400 microg L(-1), <1. These results indicate that serum ferritin level <50 microg L(-1) depict a very high probability of iron deficiency anaemia (0.83-0.99) irrespective of the patient's pre-test probability. CONCLUSION: Serum ferritin is the most powerful noninvasive test for the diagnosis of iron deficiency anaemia in patients with liver cirrhosis. It should be the primary test of choice in patients suspected of having the disease. When the level was less than 50 microg L(-1), iron supplement may be prescribed without necessitating bone marrow aspiration.

Prognostic factors of green pit viper bites.

Clinical features of green pit viper bites vary from asymptomatic to fatal bleeding. Antivenin promptly reverses the coagulopathy but has considerable adverse side effects. In this study, potential clinical predictors of severe outcomes (wound necrosis, wound infection, and systemic bleeding) and antivenin allergy were determined in 271 moderate to severe cases of green pit viper bites by multivariate analysis. The incidences of systemic bleeding, wound necrosis, secondary infection, and antivenin allergy were 17.3%, 6.6%, 5.5%, and 20.8% respectively. The predictors of systemic bleeding were the combination of thrombocytopenia and prolonged venous clotting time and bite sites away from digits. A bite on the fingers or toes was a risk factor for skin necrosis (P = 0.03). Systemic absorption of the venom from digits may be poor, resulting in severe local but mild systemic effects. The presence of blisters often led to necrosis and secondary infections (P = 0.0037 and P = 0.0006, respectively). Although negative skin test results do not exclude the possibility of antivenin allergy, positive results indicate a high risk (P = 0.016) requiring special precautions.

Anemias in Thai patients with cirrhosis.

Anemia is a frequent complication in patients with cirrhosis. Only one study has been previously reported regarding the etiology of anemias in Thai cirrhotic patients. The diagnosis of iron deficiency in the study however was not based on standard criteria. Herein we report the frequency and hematological manifestations of various causes of anemias diagnosed by using gold standard criteria in 72 consecutive Thai cirrhotic patients. The diagnosis of cirrhosis was based on the characteristic clinical features and the ultrasonographic findings. The median age of the patients was 49 years; male:female was 1:1.3. The mean hemoglobin value was 8.3 g/dl and the mean MCV was 96.6 fl. Most patients revealed macrocytosis, normal WBC count and mild thrombocytopenia. Iron deficiency, defined as absent bone marrow iron stores, was the most common anemia found in 40% of the patients while folate deficiency, diagnosed when red cell folate was < 160 ng/ml packed RBC, was documented in 10% of the patients. Megaloblastosis, hemolysis and anemia of chronic disease was found in 4%, 28% and 13% of the patients, respectively. Folate deficiency was significantly more common in the alcoholic patients (P = 0.01). Iron deficiency was thus the most common anemia in Thai patients with cirrhosis. The frequency of folate deficiency was not rare and the rate was comparable to data reported from western countries in spite of the Thai diet being relatively rich in folates.

Neurological manifestations in patients with malignant histiocytosis.

Of the 67 patients who were diagnosed with malignant histiocytosis at the Department of Medicine, Chulalongkorn Hospital, from January 1981 to May 1992, seven (10%) were found to have neurological manifestations. In five patients, neurologic diseases were the presenting clinical features. In the remaining two patients, the disease manifested at the time of relapse. Leptomeningeal infiltration, the most common pattern of involvement, was found in five patients. Involvement of the spinal cord was noted in three patients and cerebral parenchyma in two individuals. Two patients demonstrated peripheral neuropathy. Rapid clinical deterioration was observed in all patients after documentation of neurological diseases with a mean survival of 1.8 months. It is concluded that the frequency and pattern of neurological manifestations in patients with malignant histiocytosis are comparable to patients with non-Hodgkin's lymphoma. However, most patients with malignant histiocytosis manifested the neurological symptoms as an initial presentation while in non-Hodgkin's lymphoma, neurologic diseases usually manifest at the time of relapse or disease progression.

Reversible severe neutropenia after ceftriaxone.

A 57-year-old woman developed severe neutropenia during treatment of an upper urinary tract infection with intravenous ceftriaxone. The dosage was 1 g/day for 18 days. There was a return to normal granulopoiesis after the drug was discontinued.

Malignant histiocytosis: a chronic variant.

An 18-year-old woman had unusual clinical manifestations of malignant histiocytosis (MH) including a long duration of massive splenomegaly, absence of lymphadenopathy, and a number of exacerbations characterized by sudden onset of fever. During life, a definite diagnosis could not be established. The antemortem pathology of the marrow and liver was nonspecific and non-diagnostic. The diagnosis of MH was made after postmortem examination by histologic and immunohistochemical studies. The long duration of massive splenomegaly suggests that this patient could represent a chronic form of MH.

Treatment of adult acute myelogenous leukemia: a pilot study at Chulalongkorn Hospital.

Twenty-seven patients with acute myelogenous leukemia (AML), aged 15 to 65 years, were treated with standard induction remission chemotherapy and two different strategies for postremission treatment. Seventeen patients (63%) achieved complete remission (CR). Nine patients (37%) died during marrow hypoplasia. The median survival of complete remitters allocated to the intensive postremission therapy is projected to be in excess of 24 months with 53 per cent probability of remaining in CR at two years. The median remission duration for patients who entered the nonintensive postremission therapy was 11 months. Age was the major factor significantly correlated with the outcome of treatment. It is concluded that intensive curative treatment should be indicated in AML patients who are less than 30 years.

Drug-induced agranulocytosis: experience in two university hospitals.

STUDY OBJECTIVE: to describe demographic data, offending drugs, clinical features, hematological profiles, clinical course, general outcome, factors influencing fatal result and microbiological aspects DESIGN: Retrospective descriptive analysis SETTING: Two university hospitals PATIENTS: 28 patients with 31 episodes of drug-induced agranulocytosis from Chulalongkorn Hospital (1976-1988) and 24 patients with 25 episodes from Songklanagarind Hospital (1983-1989) RESULTS: Female exceeds male by ratio of 2.1:1, age ranged 15-73 years. The common drugs were antimicrobial agents, penicillins and sulfonamides; antithyroid drugs; antituberculous drugs and non-steroidal antiinflammatory drugs (NSAIDs), unidentified in 16 per cent. About 61 per cent occurred more than 14 days after drug exposure. The key presentations revealed fever, prostration and sorethroat. Two marrow appearances were recognised: left-shifted granulopoiesis with few or no mature forms (type-I) in 66 per cent; and the other, selective reduction of granulocytic precursors (type-II). Penicillins, sulfonamides, antithyroid drugs and NSAIDs were all related to type-I. The leukocyte count, neutrophil and monocyte numbers were significantly higher in type-I, as well much more rapid recovery time (mean +/- SD, 4.4 +/- 1.5 vs 12.4 +/- 14.1 days, p = 0). The possible sites of infection were identified in 59 per cent, the major ones were oral cavity and GI tract. The organisms were isolated in 58 per cent from the primary sites and 25 per cent from hemocultures, of which Pseudomonas aeruginosa was the most common. The case fatality rate is 12.5 per cent. The dead victims had the higher age, and strongly association with type-II marrow appearance (p = 0.038).

Reversible hyperpigmentation of skin and nails with white hair due to vitamin B12 deficiency.

A case of reversible generalized hyperpigmentation of the skin and nails with reversible premature gray hair due to vitamin B12 deficiency is reported. The cause of the vitamin B12 deficiency in this patient was pernicious anemia. The pigmentation of his skin and hair returned to normal after treatment with intramuscular cyanocobalamin.