A prospective evaluation of normal mean platelet volume in discriminating hyperdestructive thrombocytopenia from hypoproductive thrombocytopenia.

Bone marrow (BM) examination is the gold standard test in discriminating between hyperdestructive thrombocytopenia and hypoproductive thrombocytopenia. However, this procedure is invasive. Mean platelet volume (MPV) is simple and may be used as an alternative diagnostic test in distinguishing these two types of thrombocytopenia. All thrombocytopenic patients (platelet count: <150.0 x 10(9)/l), except those with congestive splenomegaly, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulopathy, were enrolled into the study prospectively. The mean MPV of normal Thais (7.9 fl) was tested as a cutoff value. Any thrombocytopenic patient with MPV of >7.9 fl would be presumptively diagnosed as hyperdestructive thrombocytopenia, whereas one with MPV of 7.9 fl could predict hyperdestructive thrombocytopenia with a sensitivity of 82.3% (95% CI: 70.5-90.8), a specificity of 92.5% (95% CI: 79.6-98.4), a positive predictive value of 94.4% (95% CI: 84.6-98.8), a negative predictive value of 77.1% (95% CI: 62.7-88.0), and a likelihood ratio of 11.0. In conclusion, the mean MPV of normal Thais may be used as a cutoff value in distinguishing these two types of thrombocytopenia.

Treatment of myelodysplastic syndrome with low-dose human granulocyte colony-stimulating factor: a multicenter study.

The objective of this study was to determine the hematopoietic effects and toxicity of low-dose granulocyte colony-stimulating factor (G-CSF) in myelodysplastic syndrome (MDS) patients with neutropenia. Recombinant human G-CSF (Lenograstim) was administered by daily subcutaneous injection with an initial dosage of 0.5 microg/kg per day for 2 weeks. Patients not responding to the initial dosage received the escalated dosage, 1 to 2 microg/kg per day for 2 weeks. Eligibility criteria were the following: French-American-British disease classification subtype refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) with an absolute neutrophil count (ANC) of <1.5 x 10(9)/L. Criteria indicating response to treatment were ANC of >1.5 x 10(9)/L and doubling of ANC on at least 2 occasions. Thirty-two MDS patients were recruited from 6 university hospitals. Eighteen patients had RA, 4 had RARS, and 10 had RAEB. Median age was 56.4 years (range, 28-87 years). Twenty-six patients (81.2%) had an increase in ANC from a median of 0.94+/-0.35 x 10(9)/L to 4.24+/-3.78 x 10(9)/L. Three of 6 patients who did not respond to the initial dosage responded to the escalated dosage of 1 microg/kg per day. Eighteen (81.8%) of 22 patients with RA or RARS responded compared with 8 (80%) of 10 patients with RAEB. The response rates in patients with ANCs of <0.5 x 10(9)/L. 0.5 to <1.0 x 10(9)/L, and 1.0 to 1.5 x 10(9)/L were 80%, 70%, and 88.2%, respectively. The side effects were minimal. No significant changes in hemoglobin levels or platelet counts were observed. In conclusion, low-dose G-CSF administered by subcutaneous injection is well tolerated and effective in improving neutropenia in MDS patients.

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.

Levels of serum tumor necrosis factor alpha in relation to clinical involvement and treatment among Thai adults with Plasmodium falciparum malaria.

UNLABELLED: Concentrations of tumor necrosis factor alpha (TNF-alpha) in serum were measured in 17 Thai men infected with Plasmodium falciparum malarial infections to determine whether they were affected by severity of infections or exchange transfusions. Twelve patients were considered having complicated malarial infections, eight of whom had cerebral malaria. Five patients had uncomplicated malarial infections. The results showed that malarial infection markedly raised TNF-alpha level above normal values (mean +/- SEM 406 +/- 38 vs 15 +/- 5, p = 0.004). In complicated malaria, cerebral involvement appeared to significantly increase concentration of TNF-alpha when compared to values in uncomplicated malaria (mean +/- SEM 496 +/- 64 vs 339 +/- 12, p = 0.01). Degree of parasitemia, intravenous quinine (day 0 value vs day 7 value) and exchange transfusion did not significantly affect TNF-alpha levels. CONCLUSION: Serum level of TNF-alpha is increased in Plasmodium falciparum malarial infections and may be a useful index to predict severity of malarial infection, cerebral malaria in particular.

Graft-versus-host-disease prophylaxis for matched unrelated donor bone marrow transplantation: comparison between cyclosporine-methotrexate and cyclosporine-methotrexate-methylprednisolone.

We performed a sequential study comparing two regimens, cyclosporine-methotrexate (CsA-MTX) and cyclosporine-methotrexate-methylprednisolone (CsA-MTX-MP) for graft-versus-host disease (GVHD) prophylaxis in patients undergoing matched unrelated donor bone marrow transplantation (MUD BMT). Study end-points were the development of GVHD, various infectious complications and survival. Twenty nine patients with malignant hematologic disease without HLA-compatible family donors were treated between May 1990 and November 1993. All donors were volunteers from the National Marrow Donor Program (NMDP) serologically HLA-A-A, B and DR identical. MLC reactivity and high resolution DR DNA typing were not used to exclude donors. Sixteen patients received CsA-MTX and 13 patients received CsA-MTX-MP. CsA and MTX doses were the same in both groups: CsA 1.5 mg/kg i.v. over 2h every 12h beginning the day prior to transplant (day-1) and MTX 10 mg/m2 i.v. bolus on days +1, +3 and +6 with leucovorin on days +2, +4 and +7. MP was administered at a dose of 0.25 mg/kg i.v. every 12h beginning on day +7 and increased to 0.5 mg/kg on day +14. Beginning on day +35 MP and CsA were tapered 5% per week with targeted discontinuation at 6 months. Both groups were comparable for primary disease, preparative regimen, recipient age (median 33 VS 33 years), donor age (median 39 vs 39.5 years), donor-recipient sex, donor ABO mismatch and serologic CMV positivity. All patients received similar supportive care.(ABSTRACT TRUNCATED AT 250 WORDS)

Pleomorphic large cell hemato-lymphoma (the so-called "malignant histiocytosis"): clinicopathological and immunophenotypic studies in 35 cases.

Thirty-five patients diagnosed with "malignant histiocytosis" from 1984 to 1989 were studied for clinical, laboratory, histopathological features as well as survival and response to therapy, Immunocytochemistry and immunophenotypic studies were performed in 12 cases using the paraffin immunoperoxidase method. The staining included alpha-1 antichymotrypsin, muramidase, immunoglobulins and monoclonal antibodies specific for T, B lymphocytes and macrophage. From the clinical features, responsiveness to therapy and survival, the patients were divided into 2 groups: the non-responders (25 cases) and responders (10 cases) groups. Very short median survival of 1.25 months was found in the non-responders, whereas, longer median survival of 14.15 months was found in the responder group. Important different clinical and laboratory features were observed among these two groups. Unresponsiveness to treatment; rapidly progressive pancytopenia, increased hemophagocytosis, presentation of immature cells in blood with extensive infiltration of malignant cells in the bone marrow; severe jaundice and deterioration of hepatic function accompanied by early extranodal involvement were almost exclusively observed initially in the non-responder group. Satisfactory response to treatment was observed only in the responder group. Similarity of histopathology, cytology and immunophenotype was observed in these two groups. The immunophenotypic study in 12 cases showed 5 cases of B-cell lymphoma, 3 cases of T-cell (with 1 Ki-1 -positive) lymphoma; 1 case of Ki-1 positive non-T, non-B anaplastic large cell lymphoma; and 3 cases of undetermined cell lineage. From this study, so-called "malignant histiocytosis" appears to be a disorder of heterogeneity. The immunophenotypes of malignant cells indicated that their origin belonged mostly to lymphoid cell lineage. Based on their clinical feature of the early hematogenous spread along with the distinct histopathological and immunophenotypic findings, the term "pleomorphic large cell hematolymphoma" is proposed to be used instead of the old misnomer, "malignant histiocytosis" (MH).

Diagnostic criteria and histologic grading in multiple myeloma: histologic and immunohistologic analysis of 176 cases with clinical correlation.

Diagnostic criteria in myeloma have not been completely standardized or tested for accuracy; furthermore, marrow findings of prognostic value have not been clearly identified. We studied 176 patients with myeloma to determine the relative value of marrow differential, tissue sections, and immunohistology singly or in concert in the diagnosis of myeloma and to correlate morphologic features with prognosis. Controls were patients with benign marrow plasmacytosis. Homogeneous nodules of plasma cells at least 1/2 high-power field and/or monotypic aggregates of plasma cells filling at least one interfatty marrow space correctly identified myeloma in 83.5% of cases, with no false positives. The current numerical criteria of marrow plasmacytosis > or = 10% occurred in 17.1% of the controls, and 39.7% of patients with myeloma had less than 10% marrow plasmacytosis at presentation. Myeloma was graded histologically into categories of none/minimal, moderate, and marked dysplasia on the basis of dysplastic features and mitoses; these categories correlated well with clinical outcome, with median length of survival of 32.9, 25.2, and 12.9 months, respectively (overall median length of survival of 123 patients with myeloma, 29.2 months). Packing of marrow by tumor and mitoses measuring at least 5/high-power field regardless of grade also was associated with a poor prognosis (median lengths of survival, 15.2 and 11 months, respectively). Myeloma may be diagnosed in the great majority of cases by demonstrating homogeneous nodules and/or monotypic aggregates of plasma cells in the marrow. Prognostic features were shown to include marked dysplasia, mitoses, packing of marrow by tumor, and clinical stage.

Exchange transfusion therapy in severe complicated malaria.

Nine cases of severe complicated falciparum malaria treated by exchange transfusion were studied. Eight patients survived and one patient died. Multisystemic complications were found in all cases. The CNS complications, acute renal failure, pulmonary insufficiency, jaundice, bleeding, sepsis, and DIC were found in 9, 7, 5, 7, 2, 4 and 1 cases, respectively. The fatal case presented with severe multisystemic complications together with 40% parasitemia. In eight survivors, whose parasitemia ranged from 0.3%, to 90%, had milder degrees of systemic complications. With the use of blood exchange 10-15 units, the parasitemia was decreased to less than 5% within 24 hours in all expect one who had parasitemia 90%. In comparison with the other 10 matched non-exchanged patients, there was no significant difference in survival rate between these two group (89% vs 80%). However, in the patients with ARDS the survival rate in the group who received the exchange transfusion therapy was superior (75% vs 0%). The exchange transfusion therapy is therefore strongly recommended in the treatment of malarial patients who present with parasitemia > 30% and severe systemic complications, particularly those who have severe acute renal failure or have lung complications. The amount of blood used for exchange transfusion should at least 1.2 times the blood volume for rapid removal of parasites and toxic metabolites from the circulation.

Suppression of erythroid progenitor cells during malarial infection in Thai adults caused by serum inhibitor.

The bone marrows of 21 Thai adults infected with Plasmodium falciparum malaria were cultured for CFU-E and BFU-E by using AB serum, autologous serum (parasitaemia) and autologous serum (post-parasitaemia). Six patients had no complication and 15 patients had pulmonary, renal or haematologic complications. In the non-complicated cases, sera during parasitaemia did not suppress the post-parasitaemia CFU-E and BFU-E. Post parasitaemia, there was suppression of CFU-E by parasitaemia sera. In the complicated cases, the autologous sera during parasitaemia suppressed the growth of both CFU-E and BFU-E both during and after parasitaemia (P < 0.05). The post-parasitaemia sera had neither a suppressive nor a stimulating effect. In the complicated cases, the progenitor cells cultured from the bone marrow post-parasitaemia were fewer in number than those cultured from the bone marrow during parasitaemia using the same sera. Two possible mechanisms of suppression are postulated, namely the reduction of erythropoietin or the increased tumour necrosis factor during malarial infection. Further studies to clarify this are being carried out.