Milica Colovic

Helicobacter pylori eradication can induce platelet recovery in chronic idiopathic thrombocytopenic purpura.

We prospectively investigated the prevalence of Helicobacter pylori (H. pylori) infection in a cohort of 54 adult Serbian patients with chronic idiopathic thrombocytopenic purpura (ITP), and examined the effects of its eradication on their platelet counts. H. pylori infection was diagnosed in 39/54 (72.2%) patients, using the 14C-urea breath test; and was significantly higher than in the healthy Serbian population (55% P < 0.05). H. pylori-positive patients were significantly older than H. pylori-negative patients (P = 0.006), though there were no significant differences regarding gender, disease duration, mean platelet counts, previous therapies and spleen status between H. pylori-positive and H. pylori-negative patients. Successful eradication was confirmed in 23/30 (77%) treated patients. Stable platelet recovery was registered in 6/23 eradicated patients (26.1%) and maintained for 18 months. Complete and partial remissions were achieved in two and four patients, respectively, including one highly refractory patient. A significant mean platelet recovery was seen 6 months after successful H. pylori eradication in the group of 23 patients (P < 0.05). No platelet recovery was registered in either H. pylori-negative (n = 15), untreated H. pylori-positive patients (n = 9) or H. pylori-positive non-eradicated patients (n = 7). Even though the pathogenetic mechanisms of H. pylori-induced thrombocytopenia remain obscure, the results of this small prospective study support the use of H. pylori eradication as an effective non-immunosuppressive treatment for chronic ITP.

Additional chromosome aberrations in acute promyelocytic leukemia: characteristics and prognostic influence

Patients with acute promyelocytic leukemia (APL) show other chromosome aberrations in addition to t(15;17) but their influence on the clinical outcome is still unclear. We have cytogeneticaly analyzed 43 APL patients with t(15;17)(q22;q21), treated with all-trans-retionic acid (ATRA) according to the recommendations of the European APL 91 Group. Additional chromosome aberrations were observed in 14/43 patients (33%) studied at initial diagnosis. These patients were designed as ‘complex’ karyotype group and were compared to patients with t(15;17) as a sole cytogenetic abnormality (‘simple’ karyotype group). The ‘complex’ group had significantly lower platelet count and fibrinogen level and fewer cases without significant DIC at diagnosis than the ‘simple’ group. Comparison of ‘simple’ and ‘complex’ groups showed significant difference in complete remission rate (76%vs 35.7%,P=0.0148) and early death rate (24%vs 64.3%,P=0.0141). Survival analysis showed that the presence of additional chromosome abnormalities and significant DIC had an adverse effects on prognosis (P=0.036 andP=0.041, respectively), independent on other prognostic factors. These data indicate more aggressive biological nature of leukemic cells in patients with additional chromosome aberrations. Supplementary therapeutic strategies may be required for this subgroup of APL patients.

Importance of early detection and follow-up of FLT3 mutations in patients with acute myeloid leukemia

Mutations in the fms-like tyrosine kinase 3 (FLT3) gene, such as internal tandem duplication (FLT3/ITD) in the juxtamembrane domain and point mutations in the tyrosine kinase domain, are the most common abnormalities in acute myeloid leukemia (AML). FLT3/ITD and FLT3/D835 mutations were analyzed in 113 Serbian adult AML patients using polymerase chain reaction. Twenty patients were found to be FLT3/ITD positive (17.7%). The mutations occurred most frequently in M5 and M0 subtypes of AML. They were mainly associated with the normal karyotype. All patients harboring FLT3/ITD had a higher number of white blood cells than patients without it (p = 0.027). FLT3/ITD mutations were associated with lower complete remission (CR) rate (χ2 = 5.706; p = 0.017) and shorter overall survival (OS; Log rank = 8.76; p = 0.0031). As for disease-free survival, the difference between FLT3/ITD-positive and FLT3/ITD-negative patients was not statistically significant (Log rank = 0.78; p = 0.3764). In multivariate analysis, the presence of FLT3/ITD mutations was the most significant prognostic factor for both OS and CR rate (p = 0.0287; relative risk = 1.73; 95% CI = 1.06–2.82). However, in the group of patients with the intermediate-risk karyotype, the mere presence of FLT3/ITD was not associated with inferior clinical outcome. FLT3/D835 point mutation was found in four patients (3.5%) only. Follow-up of the FLT3/ITD-positive patients revealed stability of this mutation during the course of the disease. However, changes in the pattern of FLT3/D835 mutations in initial and relapsed AML were observed. Our results indicate an association of FLT3/ITD with the adverse outcome in AML patients treated with standard induction chemotherapy. Because FLT3/ITD mutation is a target for specific therapeutic inhibition, its early detection could be helpful in clinical practice.

Correlation of sera TNF-α with percentage of bone marrow plasma cells, LDH, β2-microglobulin, and clinical stage in multiple myeloma

Tumor necrosis factor-α (TNF-α) is important for function, differentiation, and transformation of B-lymphocytes in multiple myeloma (MM) but can also induce apoptosis of myeloma cells. Based on this opposite effect, it is very crucial to analyze the correlation of the serum level of TNF-α with clinical parameters of the patients. In this article, we analyzed 18 MM patients, 48% male and 52% female, with a mean age of 52 yr (range: 35–81 yr), clinical stage I in 21.4%, stage II in 26.4%, and stage III in 52.2% of patients. Patients with advanced clinical stage, presence of osteolysis, and elevated lactate dehydrogenase (LDH) had a significant difference (Mann-Whitney U-test, p<0.05) in the serum level of TNF-α in comparison with those in the early stage, without osteolysis, and normal LDH. The correlation of individual values of TNF-α with the percentage of plasma cells in the bone marrow, LDH, β2-microglobulin, fibrinogen, and sedimentation rate was significant (p<0.05). However, we have not found a significant correlation between TNF-α and concentration of hemoglobin, the number of white blood cells or platelets (p>0.05). We concluded that our data indicate determination of TNF-α as a good parameter for estimation of tumor mass presence, among individual patients with MM, and may by used for monitoring during application of different therapy protocols.

Hypocellular myelodysplastic syndromes

The article is concerned with incidence, clinical features, response to therapy, and prognosis of patients with hypocellular myelodysplastic syndromes. Bone marrow (BM) cellularity <30% (or <20% in patients >70 yr) was found in 24 of 236 (10.2%) trephine biopsies. Median age was 61 yr, with significant male predominance (M/F=3.0) At diagnosis, median hemoglobin was 83 g/L, median platelet and neutrofil counts were 31 × 109/L and 1.2 × 109/L, respectively. According to FAB classification, 17 patients had RA, 6 had RAEB, and only 1 had RAEB-t. Beside marrow hypoplasia, the most prominent PH finding was megakaryocyte hypoplasia and dysplasia, found in two-thirds of cases, each. Comparison between hypocellular and normo/hypercellular MDS cases regarding clinicopathological features showed younger age, more severe cytopenia, less blood and BM blast infiltration, MK hypoproliferation, and more pronounced stromal reactions in former cases. Karyotypic abnormalities were present in 12.5% hypocellular cases, in contrast to 44.6% normo/hypercellular cases (p=0.0025). Eleven patients were treated with supportive therapy alone, six with danazol or androgens, six with immunosuppressive therapy, and one with LDARAC. However, complete or partial response was achieved in only four patients treated with danazol or androgens. None of the patients developed leukemia. Eleven patients died, so marrow insufficiency was the main cause of death. Median survival was 33 mo for hypocellular MDS, and 19 mo for normo/hypercellular MDS (p=0.09). The results confirm the existence of hypocellular variant of MDS, which seems to have better prognosis than those patients with normo/hypercellular disease.

Disseminated Burkitt's-like lymphoma during pregnancy

The occurrence of Burkitts-like lymphoma (BL) during pregnancy is rarely diagnosed and its outcome is poor. A case of BL localized in the uterus, ovaries and breast during the course of pregnancy is presented. The patient was treated with a combination of surgery and chemotherapy and was disease-free for 6 months after the diagnosis.

More than a third of non-gastric malt lymphomas are disseminated at diagnosis: a single center survey

Mucosa‐associated lymphoid tissue (MALT) lymphomas are extranodal B‐cell tumors that generally follow an indolent course. The gastrointestinal tract is the most common site of MALT lymphoma, comprising 50% of all cases. The tissue lesions are often localized, have high therapeutic response rates with late relapses with a long overall survival (OS). The patients with non‐gastric lesions may follow a different clinical course and many of them present with disseminated disease. This study reports a series of 51 patients with non‐gastric MALT lymphoma. Twenty patients (39.2%) presented with disseminated disease, seven (13.7%) patients had two MALT mucosal sites involved and eight (15.7%) had involvement of three or more mucosal sites. At presentation, 17 (33.3%) patients had the lymph node and 12 (23.5%) the bone marrow involvement. Following various combinations of treatment, complete remission was achieved in 40 (81.6%), and partial remission in three of the 49 treated patients with no difference in response rates between different disease stages. Relapse occurred in 12/43 (27.9%) patients among whom eight (18.6%) recurred in the presenting organ system. Five patients (9.8%) died because of a rapid disease progression after a median follow‐up of 56 months; two patients with primary lung lesions, 1 patient with secondary intestinal disease, and 2 patients suffered transformation to diffuse large B‐cell lymphoma. No significant difference in survival was found between localized and disseminated disease (log rank 0.05, df = 1, P = 0.81). A patient age ≥ 60 yr at diagnosis and presentation with the nodal disease were found to be statistically significant negative prognostic factors (P < 0.05). Median OS was not reached after 145 months of follow‐up, with the estimated OS being 88% at 2 yr, and 78% at 5 yr.

Outcomes of primary thyroid non-Hodgkin's lymphoma: a series of nine consecutive cases.

Primary non-Hodgkin’s lymphoma (NHL) of the thyroid gland is a rare disease with an incidence of 0.5 per 100,000 population. Stages IE and IIE thyroid NHL have been traditionally treated by surgical resection; however, modern treatment consists of chemotherapy and local radiotherapy, and surgery is often reserved for tissue diagnosis and relief of airway compression. We retrospectively reviewed the management and outcomes of nine consecutive patients with thyroid NHL, eight females and one male (median age 63 yr, range 34-71 yr) treated between 1994 and 1999. Five patients had disease stage IE and 4 stage IIE. Median follow-up was 72 mo. Pathohistology and immunohistochemistry identified two patients with mucosa-associated lymphoid tissue (MALT), three follicular center cell lymphoma (FCC), two patients large B-cell lymphoma (BLCL), one a marginal zone lymphoma (MZL), and one patient a peripheral T-cell lymphoma (PTCL). Total thyroidectomy was performed in three patients and subtotal thyroidectomy in four. One (MALT) patient underwent surgery alone; three patients surgery, radiotherapy, and chemotherapy (two FCC, one PTCL); three patients surgery and chemotherapy (one MALT, one FCC, one LBCL); and two chemotherapy alone (one LBCL, one MZL). Median survival was 79 mo (range 13–124 mo). The PTCL patient, a 34-yr-old man, died from disseminated disease at 13 mo despite secondary chemotherapy, and one LBCL patient with extensively invasive local disease died from stroke 17 mo after diagnosis. The remaining seven patients remain in remission with no local or systemic relapse at a mean of 86 mo. With appropriate therapy primary thyroid NHL has a favorable course; however, prognosis depends on the histology, local spread, and the stage of the disease at presentation, as well as the patient’s performance status. Surgery in combination with chemotherapy and/or radiotherapy is still warranted for intermediate and high-grade thyroid NHLs, with over 77% of patients achieving long-term remission. Peripheral T-cell lymphoma carries a poor prognosis.

Indolent course of the cutaneous Hodgkin's disease

Abstract:  Skin involvement in Hodgkins disease (HD) is most often a secondary phenomenon representing a rare, late manifestation of dissemination of the disease heralding a grave prognosis. Primary cutaneous HD is very unusual, being reported in 0.5–3.4% of all patients. Based on the introduction of immunohistochemistry for better detection and classification, we report a case with an ostensibly isolated primary cutaneous HD who developed multiple cutaneous lesions 5 years before enlargement of the lymph node involved during relapse. Pathohistology of skin lesions and the involved lymph node indeed showed the same subtype (mixed cellularity) of HD characterized by the presence of CD15+, CD30+, CD45RO– cell‐surface markers and by the presence of Epstein–Barr virus+ marker‐analyzed immunohistochemistry.

Inversion of chromosome 16 in accelerated phase of chronic myeloid leukaemia: report of a case and review of the literature

A patient with a Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) developed a blast crisis (FAB subtype AML-M2) without a monocytic involvement. Karyotype showed the presence of inv(16)(p13;q22) in addition to Ph, in 16/20 marrow metaphases.