Merve Pamukçuoğlu

Visceral Leishmaniasis Mimicking Autoimmune Hepatitis, Primary Biliary Cirrhosis, and Systemic Lupus Erythematosus Overlap

Visceral leishmaniasis (VL) is a life-threatening infection caused by Leishmania species. In addition to typical clinical findings as fever, hepatosplenomegaly, and cachexia, VL is associated with autoimmune phenomena. To date, VL mimicking or exacerbating various autoimmune diseases have been described, including systemic lupus erythematosus (SLE), rheumatoid arthritis, and autoimmune hepatitis (AIH). Herein, we presented a patient with VL who had overlapping clinical features with SLE, AIH, as well as antimitochondrial antibody (AMA-M2) positive primary biliary cirrhosis.

Hyper-CVAD regimen in routine management of adult acute lymphoblastic leukemia: a retrospective multicenter study.

Treatment of acute lymphoblastic leukemia is unsatisfactory in adults due to disease and patient-related factors and probably because adult chemotherapy regimens are weaker than pediatric protocols. Worries about inadequacy of adult regimens urged many hematologists, including us, to reconsider their routine treatment practices. In this retrospective multicenter study, we aimed to evaluate results of hyper-CVAD treatment in comparison to other intensive protocols. All patients aged ≤65 years who were commenced on intensive induction chemotherapy between 1999 and 2011 were included in the study. Sixty-eight of 166 patients received hyper-CVAD, 65 were treated with CALGB-8811 regimen and 33 with multiple other protocols. Limited number of patients who were treated with other intensive protocols and mature B-acute lymphoblastic leukemia cases who were mostly given hyper-CVAD were eliminated from the statistical analyses. In spite of a favorable complete remission rate (84.2%), overall (26.3 vs. 44.2% at 5 years, p = 0.05) and disease-free (24.9 vs. 48.2%, p = 0.001) survival rates were inferior with hyper-CVAD compared to CALGB-8811 due to higher cumulative nonrelapse mortality risk (29.7 vs. 5.9%, p = 0.003) and no superiority in cumulative relapse incidence comparison (45% for both arms, p = 0.44). Hyper-CVAD, in its original form, was a less favorable regimen in our practice.

Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents, new spectrum of infections.

Abstract Objective and importance Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6–8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients. Clinical presentation We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib. Intervention The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients. Conclusion Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.

Adverse impact of hyperferritinemia and transfusion dependency on treatment success in myelodysplastic syndrome

BACKGROUND Myelodysplastic syndrome (MDS) is characterized by peripheral cytopenias and dysplasia in one or more cell lines in the bone marrow. A significant proportion of patients require blood product support due to symptomatic anemia and/or thrombocytopenia during the course of their disease. This retrospective study was planned to evaluate the transfusion requirement of MDS patients and the role of ferritin in predicting transfusion requirement and response to treatment. METHODS We retrospectively reviewed the records of 35 MDS patients [median age: 66 (22-84); male/female: 21/14]. The World Health Organization (WHO) criteria was used for disease classification and International Prognostic Scoring System (IPSS) for risk stratification. RESULTS A total of 22 patients (62.8%) required transfusions during follow-up. While all the 22 patients received packed red blood cells (PRBCs), only 8 patients (22.9%) required platelet transfusion(s). Although no significant relationship was demonstrated between transfusion dependency and disease progression, patients who responded to disease-specific treatment were exposed to less PRBC transfusions compared to non-responders (p=0.04). Treatment response was found to be better in patients who had lower serum ferritin levels at diagnosis (p=0.004). A total of 11 patients were followed for a minimum of 24months. Transfusion load was not different among these patients with respect to disease subtype, IPSS risk score and treatment protocol in the first and second 12-month interval. Median overall survival of the cohort was 26.3 (0.4-160.3) months and median progression free survival was 24.9 (0.4-160.3) months. CONCLUSION The present report underlines the association of baseline hyperferritinemia and transfusion dependency with treatment success in MDS. Even in patients treated with new generation agents, the vicious impact of transfusion load seems to be the tender spot of the MDS puzzle. The prognostic impact of baseline hyperferritinemia should be validated with further studies.

Peripheral and bone marrow CD34+ cell levels on chronic myeloproliferative disease

ABSTRACT Purpose: The aim of the present study was to examine the relationship between peripheral CD34+ and bone marrow CD34+ levels and the clinicopathologic characteristics and laboratory parameters of myeloproliferative disease (MPD) patients. Patients and methods: A total of 103 MPD patients were enrolled in this study. We examined the relationship between bone marrow CD34+ and peripheral CD34+ levels and the patients’ clinicopathologic and laboratory parameters. Results: There were no significant correlations between the peripheral CD34+ levels and the JAK-2 V617F mutation, thrombosis, white blood cells (WBC), lactate dehydrogenase (LDH), transferrin saturation (TS), ferritin, or bone marrow cellularity. In addition, there were no significant correlations between bone marrow CD34+ levels and the JAK-2 V617F mutation, thrombosis, WBC, LDH, TS, ferritin, or bone marrow cellularity (P > 0.05). We did not identify any significant relationship between peripheral CD34+ and bone marrow CD34+ levels (P > 0.05). However, there were significant correlations between peripheral CD34+ levels and bone marrow fibrosis (P < 0.001), between bone marrow CD34+ levels and constitutional symptoms (P < 0.05), and between bone marrow CD34+ levels and bone marrow fibrosis (P < 0.001). Conclusion: We did not find any significant relationship between the clinicopathologic and laboratory characteristics and peripheral and bone marrow CD34+ cells from bone marrow fibrosis patients. There was also no significant relationship between bone marrow CD34+ cells and peripheral CD34+ cells. Some peripheral CD34+ cells may originate from the spleen rather than the bone marrow, which may given us different result of some parameters.

A Rare Case of Acute Leukemia Relapsing with a Granulocytic Sarcoma Causing Ectopic Pregnancy

A 33 year old female was admitted to department of obstetric and gynaecology with profuse vaginal bleeding. She was diagnosed with acute myeloid leukemia 3 months ago. Pelvic ultrasound was unremarkable. Since vaginal bleeding persisted despite normal platelet counts low dose methotrexate was administered with the presumptive diagnosis of ectopic pregnancy. A laparoscopic investigation was performed as she did not respond to this treatment which revealed an intraluminal ectopic pregnancy in her right fallopian tube. A pathological specimen was obtained. Granulocytic sarcoma is an infiltrate of immature granulocytic precursor cells in an extramedullary site. To best of our knowledge, this case is the third patient with GS in the fallopian tube and the first case causing ectopic pregnancy.

Non-leukemic granulocytic sarcoma presenting with multiple skin nodules and a retroperitoneal mass.

To the Editor Here we present a case of multiple granulocytic sarcomas with monocytic differentiation involving the skin and retroperitoneal area. A 19-year-old man presented with the complaints of generalized arthralgia and fixed non-tender nodular lesions (Figure 1). Physical examination revealed generalized immobile, painless violaceous erythematous nodules on his back, bilateral arms and legs, and joints. The largest nodule was 3x2 cm, located on his right posterolateral upper leg. Abnormal laboratory values included hemoglobin of 84 g/L, hematocrit of 27.2%, erythroid sedimentation rate of 58 mm/h, and lactate dehydrogenase of 613 IU/L. Blood smear revealed hypochromia and microcytosis, and bone marrow was normocellular without blasts. However, monocyte and macrophage marker CD163 was positive in 10%-15% of the bone marrow cells. The pathological examination of the nodular lesions revealed medium-sized, irregular-shaped blastic cells with frequent mitotic activity, which infiltrated the dermis. The tumor tissue contained tingible body macrophages with nuclear debris. In immunohistochemical study, these cells were positive for CD163, lysozyme, CD4, and CD43, while CD117, MPO, CD68, langerin, CD1a, S–100, CD35, CD21, clusterin, fascin, factor 13a, CD123, TCL–1, TdT, CD3, CD20, and CD30 were all negative. The Ki–67 proliferation index of the neoplastic cells was 80%. In situ hybridization study with the EBER probe for Epstein-Barr virus was negative. Figure 1 Multiple violaceous skin nodules. Abdominal and thorax computerized tomography (CT) was performed, which revealed a right retroperitoneal mass with blurred margins. A CT-guided biopsy was performed. The biopsy showed pleomorphic cell infiltration with large mononuclear and binuclear cells with clear nucleoli, which were CD163-positive, CD117-negative, and focal MPO-positive. These atypical pleomorphic, monocytic-histiocytic cells did not have blastic morphology. A high dose of cytosine-arabinoside and idarubicin was started. The nodular lesions disappeared 20 days after starting chemotherapy. Arthralgia, dyspnea, and respiratory distress developed consequently. Right pleural effusion was demonstrated in the chest X-ray. The cytological examination of the pleural fluid revealed blastic infiltration. Since the retroperitoneal mass persisted in follow-up abdominal CT, a new chemotherapy regimen containing fludarabine, cytosine arabinoside, and idarubicin was started. However, pleural effusion persisted and required Pleurocan evacuation. Methotrexate (Mtx) was given intrapleurally accompanied with systemic high-dose Mtx. Tumor lysis syndrome developed 28 days after this regimen and required intubation; the patient died due to cardiac arrest 3 days later. Granulocytic sarcoma (GS) is the tumoral infiltration of extramedullary sites with immature myeloid precursor cells; it is associated with 3%-8% of acute myeloid leukemia (AML) cases and rarely with chronic myeloproliferative disorders [1]. Monocytic differentiation of GS is seen mostly in AML M4 and M5 subtypes according to the French-American-British (FAB) classification [2]. Any extramedullary anatomic site may be involved with GS and it might rarely precede but usually occurs simultaneously with acute leukemia. CD163 positivity is controversial in GS. While Lau et al. claimed that CD163 is a highly specific marker for cells of monocyte/macrophage lineage, they did not demonstrate CD163 positivity in GS in their series [2]. Backe et al., however, demonstrated CD163 positivity in myeloid leukemias with monocytic differentiation [3], while Benet et al. demonstrated CD163 positivity in 52% of their cases of leukemia cutis [4]. The prevalence of skin involvement in myeloid malignancies is approximately 3%, and it is usually associated with cases with monocytic differentiation. It is difficult to identify the origin of the tumor when it is not associated with bone marrow infiltration, namely “aleukemic leukemia cutis” [4]. In a series of 173 patients with leukemia cutis, 7.5% of the patients with leukemic skin infiltration had no underlying myeloid neoplasm [4). Skin is one of the most common sites of involvement in GS, with approximately one-quarter of patients with GS having skin involvement [4]. The presented patient had arthralgia and multiple granulocytic nodules on various parts of the body and joints without bone morrow involvement. The morphologic appearance of the skin lesions was typical for leukemia cutis in its color and nodular form, as is immunohistochemistry with monocytic differentiation. Nevertheless, most of the aleukemic GS of skin is known to be associated with infiltration with cells of monocytic differentiation [5]. In conclusion, myeloid leukemias might present with granulocytic sarcomas, particularly in skin without bone marrow involvement. Multiple skin lesions of nodular pattern with violaceous color might suggest an underlying myeloid neoplasm. The positivity of monocytic markers such as CD68 and CD163 is typical for leukemia with a predilection to the skin. Patients with aleukemic granulocytic sarcoma might have a very aggressive course, with evolution to tumor lysis syndrome. Conflict of Interest Statement The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affiliations relevant to the subject matter or materials included.