A 2-Year, Longitudinal, Prospective Study of the Effects of Eltrombopag on Bone Marrow in Patients with Chronic Immune Thrombocytopenia.

BACKGROUND: The long-term effects of eltrombopag on bone marrow (BM) reticulin and/or collagen deposition in previously treated adults with chronic immune thrombocytopenia (ITP) were assessed. METHODS: Three BM biopsies were collected at baseline and after 1 and 2 years of eltrombopag treatment. Specimens were centrally processed, stained for reticulin and collagen, independently reviewed by 2 hematopathologists, and rated according to the European Consensus 0-3 scale of marrow fibrosis (MF). RESULTS: Of 162 patients enrolled, 93 completed all 3 protocol-specified BM biopsies. All patients with a baseline assessment were negative for collagen. Of 159 patients assessed at baseline, 150 (94%) had normal reticulin (MF-0) and 9 (6%) had minimally increased reticulin (MF-1). After 2 years, 83/93 patients (89%) with BM biopsies had MF-0, 10 (11%) had MF-1, and none had MF-2 or MF-3. Five out of 127 patients (4%) at 1 year and 1 out of 93 (1%) at 2 years had collagen deposition. None of the patients had clinical symptoms typical of BM dysfunction or abnormalities of clinical concern based on white blood cell count or peripheral blood smear. CONCLUSION: For most patients with chronic ITP, eltrombopag is not associated with clinically relevant increases in BM reticulin or collagen formation.

Evaluation of bone marrow reticulin in patients with chronic immune thrombocytopenia treated with eltrombopag: Data from the EXTEND study.

Thrombopoietin receptor agonists, which raise platelet counts in patients with chronic immune thrombocytopenia, may be associated with increases in bone marrow (BM) reticulin. Patients with chronic immune thrombocytopenia participating in the Eltrombopag Extended Dosing (EXTEND) study underwent BM biopsies to identify clinically relevant BM fibrosis-related increases. Specimens were centrally reviewed by 2 hematopathologists. Two hundred thirty-two biopsy specimens were collected from 117 patients treated for ≤5.5 years. Moderate to marked reticulin fibrosis was found in 2 patients. After withdrawing from the study, the biopsy of 1 patient reverted to normal. There were no other pathologic changes identified among on-treatment specimens, and no pattern of abnormal reticulin deposition associated with eltrombopag treatment was evident.

Systemic mastocytosis associated with t(8;21)(q22;q22) acute myeloid leukemia.

Although KIT mutations are present in 20-25% of cases of t(8;21)(q22;q22) acute myeloid leukemia (AML), concurrent development of systemic mastocytosis (SM) is exceedingly rare. We examined the clinicopathologic features of SM associated with t(8;21)(q22;q22) AML in ten patients (six from our institutions and four from published literature) with t(8;21) AML and SM. In the majority of these cases, a definitive diagnosis of SM was made after chemotherapy, when the mast cell infiltrates were prominent. Deletion 9q was an additional cytogenetic abnormality in four cases. Four of the ten patients failed to achieve remission after standard chemotherapy and seven of the ten patients have died of AML. In the two patients who achieved durable remission after allogeneic hematopoietic stem cell transplant, recipient-derived neoplastic bone marrow mast cells persisted despite leukemic remission. SM associated with t(8;21) AML carries a dismal prognosis; therefore, detection of concurrent SM at diagnosis of t(8;21) AML has important prognostic implications.

Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: analysis of clinicopathologic features and activating c-kit mutations.

The majority of patients with systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD) have a myeloid stem cell malignancy including myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative disorders, acute myeloid leukemia (AML), or chronic myeloproliferative disease. The clinicopathologic features of SM-AHNMD have not been fully characterized. We describe seven cases of this entity: 3 with MDS, 3 with AML, and 1 with chronic myelomonocytic leukemia. In the majority of cases, SM was diagnosed concurrently with the myeloid malignancy and aberrant mast cell morphology was observed. The commonly described c-kit enzymatic site mutation Asp816Val was detected only in 2 cases, while 3 patients carried the Asp816His mutation. Among the 3 cases with AML, 2 patients carried the translocation t(8;21). On the basis of our results and other reported cases, there appears to be a specific association between SM and AML with t(8;21). Concurrent occurrence of SM may define a subset of patients with de novo AML and other myeloid malignancies who have an adverse prognosis. As clinically effective tyrosine kinase inhibitors that inhibit enzymatic-type c-kit mutations are being developed, detection of mast cell proliferation associated with myeloid malignancy may have important therapeutic implications.

A clinical and epidemiological study of an epidemic of non-A non-B hepatitis in Rangoon.

A total of 519 cases of viral hepatitis were admitted to the Infectious Diseases Hospital from June to October 1982 during an epidemic in Rangoon; 399 cases were found to be hepatitis non-A non-B, 84 cases were hepatitis B and 36 cases were hepatitis A. A clinical study was done of the 399 non-A non-B hepatitis cases. Also a prospective study of 434 households made up of 217 non-A non-B hepatitis cases with their families, together with 217 matched control families were followed up for a period of seven months to detect secondary cases among the family members. Non-A non-B hepatitis was found to occur most in adults of 20-40 years. Non-A non-B hepatitis is indistinguishable from the other two types of viral hepatitis. Case fatality rate was the highest in pregnant women with non-A non-B hepatitis. The field study suggested non-A non-B hepatitis can be transmitted by intrafamily spread. No evidence of sexual or syringe transmission of non-A non-B hepatitis was found.

Epidemiology and transmission dynamics of Ascaris lumbricoides in Okpo village, rural Burma.

A horizontal study of the prevalence of Ascaris infection was carried out on the total population of Okpo village near Rangoon, Burma, where a similar study had been conducted 13 years earlier. Ascaris eggs in faeces were counted after treatment with levamisole on a random sample of 50% of the infected population to give information to the numbers of epg of stool, the mean worm burden per host and the distribution of worms in the community. The information on prevalence is compared with that of the previous survey. Various population parameters of Ascaris were calculated to estimate the transmission dynamics of A. lumbricoides. In addition, chemotherapeutic regimes, assessed on the proportion of the human population to be treated and the time interval between treatments, are proposed to reduce transmission below a critical threshold. The findings are compared with those of other studies and the probable mode of occurrence and maintenance of Ascaris infection in Okpo village are discussed.

Risk factors of breast cancer in Burma.

A hospital-based case-control study of breast cancer was undertaken in Rangoon. The age-standardized incidence rate, 25.1 per 100,000 woman-years and the shape of the age-incidence curve show that Rangoon women have an intermediate level of breast cancer risk compared to women of other countries in the world. The analysis is based on 193 cases and 400 controls. Breast cancer risk was found to be directly related to educational attainment. There was an increased risk associated with early menarche and late menopause. The most striking finding was the strong inverse relationship between risk and parity; women who had six or more children have only one-third the breast cancer risk of married women who had less than four children. This association is not confounded by case-control differences in age at birth of first child. The association of breast cancer risk with age at first birth was not striking; only women with a first birth after age 30 were at increased risk. Breast cancer risk was unrelated to lactation. Overall, the epidemiology of breast cancer in Burma is similar to that in most other countries. However, the possibility of an unusual relationship of risk to parity and age at first parturition warrants further exploration.