Positive and negative predictive values of HLA-DR and CD34 in the diagnosis of acute promyelocytic leukemia and other types of acute myeloid leukemia with recurrent chromosomal translocations.

The predictive value of HLA-DR and CD34 in the diagnosis of four distinct genetic entities of acute myeloid leukemia (AML) is presently not established. We evaluated the positive and negative predictive values (PPV and NPV, respectively), sensitivity, specificity, and correlation coefficients of HLA-DR and CD34 in AML pa-tients with t(15;17), t(8;21), inv(16), and abn(11q23). In AML with t(15;17) (n = 64), HLA-DR was expressed in 4.68% and CD34 was expressed in 15.62% and none of the cases expressed both HLA-DR and CD34. In AML with t(8;21) (n = 99), HLA-DR, CD34 or both antigens were expressed in the majority of cases (90.90%, 80.80%, and 79.79%, respectively). AML patients with inv(16) (n = 18) and abn(11q23) (n = 31) also highly expressed HLA-DR and CD34. Eight cases of t(8;21) and 1 case of abn(11q23) did not express either antigen. The highest corre-lation between CD34 and HLA-DR expression values was observed in cases with t(8;21) (r = 0.72) with the lowest correlation in inv(16) (r = 0.035). The PPV and NPV of HLA-DR-negativity plus CD34-negativity to predict t(15;17) was 85% and 100%, respectively, with 100% sensitivity and 92.74% specificity. The PPV and NPV of other mye-loid markers such as CD117, MPO and CD11c to diagnose t(15;17) were much lower than those of HLA-DR and CD34. It was concluded that the absence of double negativity of HLA-DR and CD34 strongly predicts against t(15;17). Rare HLA-DR-positive/CD34-negative cases exist in patients with t(15;17) and 8% of t(8;21) cases ex-pressed neither antigen. Further studies should determine whether HLA-DR-positive t(15;17) and HLA-DR-negative/CD34-negative t(8;21) represent a special entity associated with significant prognostic relevance.

Clinical presentation and outcome of Thai patients with chronic lymphocytic leukemia: retrospective analysis of 184 cases.

Chronic lymphocytic leukemia (CLL), which is the most common leukemia in adult population in the Western world, is surprisingly rare in Thailand. The objective of our study was to retrospectively analyze the clinical presentations and outcome of a large cohort of Thai CLL patients diagnosed at a single institution in Bangkok, Thailand, from 1963-1998. One hundred and eighty-four patients were included in the study. The most frequent age group was 60-80 years old with the male to female ratio of 2:1. Only 12% of patients were younger than the age of 50. Most patients were from the central agricultural region of Thailand. Clinical findings at presentation included splenomegaly (64%), lymphadenopathy (60%), anemia (54%), hepatomegaly (49%), fatigue (39%), weight loss (33%), fever (21%), thrombocytopenia (18%), and anorexia (8%). Only 8% of Thai CLL patients were asymptomatic at presentation. The majority of patients were categorized as stages III and IV with the median survival of 20 months and 8 months, respectively. Infection was the most common cause of death, particularly in the elderly patients who had comorbid illnesses. Twenty-two percent of the patients had associated autoimmune disorders. The unfavorable prognostic factors observed were older age (> 70 years), weight loss and hepatosplenomegaly. We concluded that the age and gender of Thai CLL patients were similar to those of the Western countries but our patients came to medical attention at a later and more advanced stage. Prospective studies at a multi-center level in Thailand should be pursued to investigate further the genetic and epidemiologic nature of Thai CLL patients.

Gastrointestinal lymphoma in Thailand: a clinicopathologic analysis of 120 cases at Siriraj Hospital according to WHO classification.

Clinicopathologic information of gastrointestinal (GI) lymphoma in Southeast Asia is lacking. A retrospective analysis of 120 cases of GI lymphoma in Thailand diagnosed at Siriraj Hospital based on WHO classification was performed. All were non-Hodgkin lymphoma (NHL). The peak age was in the sixth and seventh decades; a slight male preponderance was observed. Sites of involvement included stomach (49.2%), intestine (46.7%), and multiple sites (4.2%). There were 104 cases of primary GI lymphoma (86.7%) and 16 cases of secondary GI lymphoma (13.3%). Presenting GI symptoms were more common in the former; while superficial lymphadenopathy and fever were more common in the latter. Mass lesions were observed in both groups (72.1% vs 56.3%). Localized and advanced diseases were found in 68.3% and 31.7% of primary GI lymphomas, respectively. The most common type of lymphoma in both groups was diffuse large B-cell lymphoma. Lymphoepithelial lesions (LEL) were not significantly different between the two groups (58.2% vs 42.9%), but Helicobacterpylori infection was significantly associated with primary gastric lymphoma (p < 0.0001). The treatment of choice for localized primary GI lymphoma is controversial. Complete surgical resection may increase the chance of complete remission, but mortality and relapse rates might be higher than those observed with combination chemotherapy alone. GI lymphomas in Thailand are mostly primary B-cell NHL. LEL is not indicative of primary GI lymphoma, but H. pylori infection is closely associated with primary gastric lymphoma. A prospective study to determine the treatment of choice for localized GI lymphoma is needed.

Monosomy 7 in patients with aplastic anemia and paroxysmal nocturnal hemoglobinuria with evolution into acute myeloid leukemia.

We report two cases of Thai patients with aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH) who subsequently developed acute myeloid leukemia (AML) at their terminal phase. Monosomy 7 was demonstrated upon karyotypic analysis of bone marrow in both cases at the time leukemia developed The first patient was a 25-year-old man diagnosed with AA at age 14, recovered from AA at age 15, developed PNH at age 21 and turned into AML at age 25. The second patient was a 27-year-old man diagnosed with PNH at age 22, developed severe AA at age 25 and turned into AML at age 27. This latter patient received anti-lymphocyte globulin when he developed severe AA but did not respond well whereas the first patient fully recovered from AA with anabolic hormone treatment. Time to diagnosis of AML in the patient who received immunosuppressive therapy was strikingly shorter than that who received conventional androgen therapy (2 years vs 11 years after AA, respectively). The presence of monosomy 7 in leukemic cells of both patients emphasizes its central role in the development of AML from AA/PNH. However, other factors such as choice of AA/PNH therapy and patients response may modulate the time to emergence of monosomy 7-carrying AML clone and frank leukemia. Further studies into the biologic and genetic mechanisms involved in the development of leukemic clone arising from AA/PNH should be explored.

Thrombocytopenic purpura associated with miliary tuberculosis.

The authors report a case of thrombocytopenia associated with miliary tuberculosis. The patient was a 28-year-old woman who was admitted because of massive upper gastrointestinal hemorrhage and acute respiratory failure. Chest radiographs revealed diffuse bilateral reticulonodular infiltration and complete blood count was significant for severe thrombocytopenia. Bone marrow biopsy was performed to investigate the cause of thrombocytopenia and demonstrated multiple tiny caseating granulomas suggesting miliary tuberculosis (TB). She received anti-TB therapy and a short course of steroid with good response. Platelet count returned to normal limit within 10 days. Although isolated thrombocytopenia is uncommon in TB, it is still important to consider TB in the differential diagnosis of thrombocytopenia, particularly in patients with abnormal chest radiographs. Bone marrow examination is very helpful in this situation.

Immunophenotypic profile of adult acute myeloid leukemia (AML): analysis of 267 cases in Thailand.

Little data exists in Thailand and other Southeast Asian countries regarding the biological characteristics of adult acute myeloid leukemia (AML). In this study, we performed a flow cytometric analysis of 267 Thai adult AML cases to delineate the pattern of leukemic cell surface antigens. Forty-eight cases (18%) were identified as acute promyelocytic leukemia (M3) and 219 cases as non-M3. The most frequent subtype of AML in Thailand was M1/M2 and the least frequent was M7. M3 immunophenotypes were characterized by their unique lack of expression of CD34 and HLA-DR as contrast to the high mean expression of 50% and 70%, respectively, in non-M3. Overall, 60% of cases expressed CD34. Aberrant lymphoid antigens were uniquely seen in specific subtypes of Thai AML, including CD19 (33% of non-M3 vs 23% of M3) and CD2 (12% of M3 vs 2% of non-M3). CD56 was frequently expressed in both M3 and non-M3 while CD16 appeared to be associated with M4/M5 (24% of cases) and CD7 with M1/M2 (21% of cases). Eighty-one percent of non-M3 expressed CD38 while only 53% of M3 did. We found that most Thai adult AML patients were on average 15-20 years younger than those of the West or Japan with only 25% of Thai cases over 60 years of age, although the immunophenotypes were not markedly different. Biological studies of acute leukemia in various countries should help to provide epidemiological clues that play a role in the pathogenesis of leukemia in different geographic regions of the world. Our study represents the largest series of AML ever investigated in the Southeast Asian region.

Reversal of marrow fibrosis in agnogenic myeloid metaplasia by allogeneic peripheral blood stem cell transplantation.

Agnogenic myeloid metaplasia (AMM) is a clonal hematopoietic stem cell disorder characterized by bone marrow fibrosis, extramedullary hemopoiesis, splenomegaly and a leukoerythroblastic blood picture. Current standard therapies using hydroxyurea, interferon, androgens or corticosteroids have not shown to prolong survival of patients with AMM. In this study, we performed a curative approach using an HLA-matched sibling as a donor for allogeneic peripheral blood stem cell transplantation (PBSCT) for a 45-year-old woman with AMM. Busulfan and cyclophosphamide were given as a conditioning regimen from day -7 to day -2 with cyclosporinA and methotrexate as post-transplant immunosuppressive therapy. Donor PBSCs were mobilized by G-CSF at 16 microg/kg/day for five days and transplantation was performed on March 2-3, 2000. The patient rapidly engrafted within 2 weeks after PBSC infusion without evidence of graft versus host disease. Her blood counts and bone marrow 2 years after transplantation were normal with full donor pattern by molecular analysis. In conclusion, marrow fibrosis can be reverted to normal by allogeneic PBSCT. Allogeneic PBSCT should thus be offered to AMM patients if an HLA-matched sibling is available. This report represents the first SCT for AMM in Thailand.

Outcome of febrile neutropenia in patients with leukemia and lymphoma in Siriraj Hospital.

One-hundred and forty-nine patients treated between January and June,1998 were reviewed. One-hundred and forty-seven patients received chemotherapy. A total of 352 cycles of chemotherapy were given with 64 episodes of documented febrile neutropenia. The median age was 35 years in acute leukemia (range 11-73) and 53 years in lymphoma (range 12-85). Twenty-two episodes of febrile neutropenia occurred in females and 42 episodes occurred in males. Fifty-six episodes occurred in patients with acute leukemia (88%), and the remainder in patients with lymphoma (12%). The incidence of febrile neutropenia in our patients with acute leukemia was 59% and less than 1% in patients with lymphoma. Eighteen episodes had positive cultures (28%); of these 14 episodes had bacteremia. The most frequent organisms identified were Pseudomonas aeruginosa (2-bacteremia) and E. coli (2-bacteremia and 1-bacteriuria). Other Gram-negative organisms were K. pneumoniae (1-bacteremia and 1-pneumonia), Enterobacter cloacae (1-bacteremia and bacteriuria), nonfermentative GNB (1-bacteremia), Proteus mirabilis (1-bacteremia), Aeromonas hydrophilla (1-bacteremia) and Acinetobacter (1-bacteriuria). Other organisms were Gram-positive bacteria, Staphylococcus aureus and group A Streptococcal bacteriuria. One BAL fluid culture was positive for Candida albicans. The overall mortality rate was 26.4% (18 deaths in 147 patients:16-acute leukemia and 2-lymphoma patients). Seventy-four percent of febrile neutropenic episodes resolved without serious morbidity after empirical antibiotic treatment. The most frequent antibiotic regimen used in this series was a combination of ceftazidime and amikacin.