Berksoy Sahin

Sweet's syndrome associated with G-CSF

Summary. Sweets syndrome (SS) developed in two patients with acute myeloid leukaemia (AML) treated with granulocyte colony stimulating factor (G‐CSF) for febrile neutropenia due to AML chemotherapy. Fever, painful skin and conjunctival lesions developed and neutrophilic infiltration was detected at biopsy specimens. Neutrophilia was not detected. Skin lesions regressed within 1–2 weeks and conjunctival lesions within 4 weeks following the cessation of G‐CSF. We conclude that SS may be a complication of G‐CSF therapy and tender skin and/or conjunctival lesions developing during G‐CSF therapy should suggest the possibility of SS.

Prognostic Significance of Microvessel Density and Vascular Endothelial Growth Factor (VEGF) Expression in non-Hodgkin's Lymphoma

Angiogenesis has a major role in the pathogenesis of malignancies. Studies involving the role of angiogenesis have been most commonly performed in solid tumors. However, studies related to hemapoietic neoplasia and angiogenesis are relatively limited. We investigated the role of angiogenesis in non-Hodgkins lymphomas (NHLs) and its relation with clinical and histopathologic prognostic indicators. In this respect, angiogenesis markers were evaluated in 71 patients with NHL and these were compared with other prognostic indicators including age, gender, histological grade, stage, extranodal involvement and survival. Microvessel density (MVD) using Factor VIII monoclonal antibody and vascular endothelial growth factor (VEGF) using monoclonal antibody for VEGF expression were studied in paraffin-embedded tissue samples. We did not find a significant relationship between MVD and patient characteristics including age, gender, stage, histological grade, nodal status, international prognostic index (IPI), and response to treatment. MVD was found to be greater in cases with B symptoms compared to those without B symptoms (14.6 ± 5.7 and 11.4 ± 5.3, respectively, p = 0.002). No significant relationship was found between VEGF and age, gender, stage, histological grade, IPI, and overall survival. The complete and partial response rate to therapy was significantly higher in VEGF-negative patients than in the VEGF-positive patients (p = 0.003). In conclusion, there appears to be a role for angiogenesis and angiogenic factors in NHLs. The combination of anti-angiogenic drugs with conventional anti-neoplastic treatment will probably be used in the future. Larger series of patients are needed to determine the prognostic value of angiogenesis in NHL.

Mucormycosis‐associated fungal infections in patients with haematologic malignancies

Among patients with haematologic disorders, mucormycosis most commonly occurs in those with acute leukaemia or lymphoma who have developed neutropenia due to malignancy or to chemotherapy, and in transplanted patients receiving immunosuppressive treatment. Here, we aim to present a retrospective study conducted over a 5‐year period (2001–2005). The study included 20 patients with haematologic malignancies with a proven mucormycosis admitted in Medical Oncology Divisions in Cukurova University Hospital. The most frequent sites of infection were paranasal sinuses (95%) and lung (5%). Antifungal treatment was empirically administered in 18 (90%) patients; 18 patients underwent radical surgical debridement (90%). The therapy was successful for only eight patients (40%). Eleven patients died within 1 months of the diagnosis of fungal infection: the cause of death was only by mucormycosis in four patients (36.6%), mucormucosis and systematic inflamatuar response syndrome (SIRS) in two patients (18.2%) and progression of haematologic disease in five patients (45.5%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: amphotericin B treatment, neutrophil recovery from postchemotherapy aplasia. At multivariate analysis, the factors that significantly correlated with recovery from infection were the liposomal amphotericin B treatment (p = 0.026), doses of L‐AmB (p = 0.008) and the length of the treatment (p = 0.01), respectively. It seems to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.

Sweet's syndrome accompanying leukaemia: seven cases and review of the literature

Seven patients with Sweets Syndrome (SS) accompanying leukaemia are presented. Six had acute myeloid leukaemia and one chronic myeloid leukaemia. SS developed during G-CSF therapy in two patients and following long periods of chemotherapy-associated neutropenia in two. This finding may suggest a possible role of G-CSF in the pathogenesis of SS. SS was diagnosed during the first presentation of three patients with leukaemia. Skin lesions on the lower extremities in two patients, widespread distribution in one, a local infiltration at the inguinal region and pleural effusion in one were interesting findings in our patients which are not usual for classical SS.

IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience.

We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/μL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.

Expression of soluble CD27 and interleukins-8 and -10 in B-cell chronic lymphocytic leukemia: Correlation with disease stage and prognosis

Investigators in this study explored levels of soluble CD27 (sCD27), interleukin (IL)-8, and IL-10 in B-cell chronic lymphocytic leukemia (B-CLL), and the correlation of these levels with disease stage and prognosis. Plasma IL-8, IL-10, and sCD27 levels were assessed with enzyme-linked immunosorbent assay tests in 22 healthy donors and 70 patients with B-CLL (49 men and 21 women). Mean patient age was 61.57 y (range, 44–75 y). Mean healthy donor age was 62.09 y (range, 40–72 y). In the study group, mean values were as follows: plasma IL-8, 284.758 pg/mL (0–1000 pg/mL); plasma IL-10, 26.152 pg/mL (0–100 pg/mL); sCD27, 731.357 U/mL (139.9–1000 U/mL); white blood cell count, 59.9 × 109/L (0.8–250.0 × 109/L); hemoglobin count, 11.2 g/dL (5.0–16.2 g/dL); platelet count, 162.5 × 109/L (29.8–317 × 109/L); B2 microglobulin (B2M) 3350.2 mg/L (274.7–7499.9 mg/L); CD38, 19.5%; and lactate dehydrogenase (count, 497.5 U/L (263.0–1507 U/L). Patients represented all Rai stages, with 22.9% at stage 0, 11.4% at stage I, 11.4% at stage II, 41.4% at stage III, and 12.9% at stage IV. Plasma levels of IL-8, IL-10, and sCD27 were correlated between study and control groups; significantly higher IL-8 (P=.001) and sCD27 (P=.000) levels were found, but the IL-10 level was not significant (P=.139). Plasma IL-10 (P=.01) and sCD27 (P=.008) were positively correlated with Rai stage, but IL-8 was not (P=.146). Levels of sCD27 were significantly correlated with values for B2M (P=.000), hemoglobin (P=.028), lactate dehydrogenase (P=.001), CD19 (P=.03), and IL-10 (P=.000). IL-8 was significantly correlated with white blood cell (P=.000) count, and CD38 (P=.001) and CD5 (P=.006) levels. IL-10 was significantly correlated with B2M (P=.017), CD19 (P=.000), platelet (P=.002), and CD27 (P=.000). In survival distributions for CD27, IL-8 and IL-10 were found to have more significant relationships for all parameters (P=.0000). In conclusion, the authors suggest that sCD27, IL-8, and IL-10 are more significant prognostic factors for B-CLL when compared with others, and these values should correlate with new prognostic factors (eg, zeta-associated protein-70, mutated/unmutated immunoglobulin variable heavy chain).

Granulocytic sarcoma of the heart: Extramedullary relapse of acute myeloblastic leukemia after allogeneic stem cell transplantation successfully treated by chemotherapy alone

We present a case of granulocytic sarcoma (GS) of the heart. A 28-year-old man with relapsed acute myelogenous leukemia (AML-M2) had undergone a non-myeloablative allogeneic peripheral stem cell transplantation. Three years following transplantation, masses were evidenced in his heart by echocardiography but had completely disappeared following a common chemotherapy etoposide, mitoxantrone, ara-C (EMA) regimen for relapsed AML. The involvement of the heart with GS is very rare and this is the first case of extramedullary disease in the heart after allogeneic transplantation. Here we present the case history and related literature has been reviewed.

Vasculitis Associated with All Trans Retinoic Acid (ATRA) in a Case with Acute Promyelocytic Leukemia

All trans retinoic acid is the drug of choice in the treatment of acute promyelocytic leukemia. But this drug has some side effects, some of which may be life-threatening. Retinoic acid syndrome is the most frequent and dangerous side effect of this differentiation inducing agent. Other side effects include Sweets syndrome, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum, granulomatous proliferation and some pulmonary complications. Here, we report vasculitis in a case with APL treated with ATRA and review the literature.

Extramedullary relapse in the pleura in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic leukemia with specific clinical, morphologic and genetic features and a good response to all trans retinoic acid (ATRA). However, extramedullary (EM) relapse is an interesting feature of these cases, especially those treated with ATRA. Recently, we have encountered an EM relapse in the pleura in a case with APL receiving an ATRA containing regimen. This case is reported and the relevant literature is reviewed.

121 P - Hepatosteatosis and alterations of CA15.3 and CEA in patients with breast cancer receiving tamoxifen

The purpose of this report was to determine if ultrasonographically documented hepatic steatosis would alter the levels of serum CA15.3 and CEA in breaat cancer-patients receiving tamoxifen. We measured aerum CA15.3, CEA, AST, ALT, alkaline phosphatase, HDL, and LDL levels in 51 patients with steatosis and in 68 without steatoais. Patients who had metastasis were excluded. One hundred ninety four CA15.3 and 193 CEA measurements for steatotic group and 154 CAIS.3 and 184 CEA measurements for non-steatotic group were performed. Two times higher levels of CA15.3 and CEA were found to be more frequent in steatotic group (30% versus 14% and 53% versus 5%, respectively). Median duration of tamoxifen usage were longer in steatotic group (49 months versus 21 months). There were no significant differences in liver enzymes and lipid levels between steatotic and non-steatotic groups. We suggested that tamoxifen may be responsible for the ultrasonographically documented hepatic steatosis in patients with breast cancer.