Erman Öztürk

Azacitidine versus decitabine in patients with refractory anemia with excess blast—Results of multicenter study

The present study aimed to compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndrome (MDS). A total of 88 patients diagnosed with refractory anemia with excess blast (RAEB) treated with azacitidine (n=57) or decitabine (n=31) were evaluated. Comparisons between azacitidine and decitabine groups were performed in the whole cohort, and in a 1:1 propensity score-matched cohort in order to reduce the simple selection bias. Patients who received azacitidine or decitabine had comparable overall response rates in both the unmatched (49.1% vs. 64.5%, p=0.166) and the propensity-matched cohorts (52% vs. 68%, p=0.248). The cumulative incidence of AML transformation at one year was comparable between azacitidine and decitabine in the unmatched (24.0% vs. 31.3%, p=0.26) and in the propensity-matched cohorts (18.7% vs. 31.5%, p=0.11). There was no difference in terms of transfusion requirement, febrile neutropenia episodes or the need for antifungal use during the treatment cycles in the propensity-matched cohort. The median overall survival was 20.4 months for azacitidine and 16.8 months for decitabine (p=0.59). Finally, we found that at least a four-cycle treatment with any HMA was a favorable factor. In conclusion, both azacitidine and decitabine have similar efficacy and toxicity profiles in the treatment of MDS-RAEB.

Sticky Platelet Syndrome in Patients with Uninduced Venous Thrombosis

Objective: Sticky platelet syndrome (SPS) is a common autosomal dominant inherited platelet disorder. SPS is characterized by platelet hyperreactivity and is associated with arterial and venous thrombosis. The aim of this study was to determine the role of SPS in patients with uninduced venous thrombosis. Material and Methods: The study included 28 patients (15 male and 13 female) with uninduced venous thrombosis. SPS was defined according to Mammen’s aggregation method, which is described in detail elsewhere. Results: According to the defined ranges for platelet hyperreactivity, 3 (50%) patients, 2 (33%), and 1 (17%) (n =6 [21%]) with a confirmed diagnosis were classified as type II, I, and III SPS, respectively. In 1 patient SPS was the only hereditary abnormality noted. The other 5 patients carried other inherited coagulation defects, in addition to SPS. Conclusion: The present findings indicate that the prevalence of SPS was 21% in the patients with uninduced venous thrombosis. We therefore suggest that SPS should be considered in the differential diagnosis of such cases. Conflict of interest:None declared.

Comparison of International Prognostic Index and NCCN-IPI in 324 patients with de novo diffuse large B-cell lymphoma: a multi-center retrospective analysis.

Erman Öztürk, Murat Özbalak, Selin Berk, Işıl Erdoğan, Emin Avşar, Anıl Dolgun, Mustafa Çetiner, Nil Molinas Mandel, Fevzi Fırat Yalnız, Tuğrul Elverdi, Ayşe Salihoğlu, Ahmet Emre Eşkazan Muhlis Cem Ar, Şeniz Öngören, Zafer Başlar, Yıldız Aydın, Teoman Soysal & Burhan Ferhanoğlu Division of Hematology, Department of Internal Medicine, Koç University, School of Medicine, Istanbul, Division of Hematology, Department of Internal Medicine, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Division of Oncology, V.K.V. American Hospital, Istanbul, Department of Biostatstics, Hacettepe University, Ankara, and Division of Oncology, Department of Internal Medicine, Koç University, School of Medicine, Istanbul, Turkey

Use of fluorodeoxyglucose positron emission tomography for diagnosis of bleomycin-induced pneumonitis in Hodgkin lymphoma

Abstract Bleomycin is an antineoplastic agent causing fatal pulmonary toxicity. Early diagnosis of bleomycin-induced pneumonitis is crucial to prevent irreversible damage. Pulmonary function tests are unreliable for identifying risk of bleomycin toxicity. Fluorodeoxyglucose PET/CT scanning can reveal inflammation secondary to pneumonitis but is not sufficiently specific for diagnosis. We retrospectively analyzed scans from 77 patients with Hodgkin lymphoma (median age 41 years, mean bleomycin dose 134 mg) to evaluate bleomycin-induced pneumonitis. We identified 13 patients with abnormal lung uptake of fluorodeoxyglucose. Tracer activity was predominantly diffuse, bilateral, in the lower lobes and subpleural areas. Interim scanning during treatment revealed pneumonitis in eight of 13 patients (asymptomatic in six). One asymptomatic patient died of bleomycin toxicity. For remaining 12 patients, bleomycin was discontinued and methylprednisolone given, all showed resolution of the pneumonitis. These findings suggest that routine interim or end-of-treatment FDG-PET/CT scanning could be beneficial for alerting clinicians to asymptomatic bleomycin-induced toxicity.

Successful treatment of a bullous urticaria with omalizumab.

Bullous form of urticaria is uncommon; there are only a few case reports in the literature. Bullous lesions can occur as a complication of spontaneous urticaria or delayed pressure urticaria. Despite many clinical and experimental researches in chronic urticaria, the etiopathogenesis of bullous urticaria is still unclear.1-4 It is thought to result from mechanical pressure of the oedema in the dermis.4 Treatment of bullous urticaria is a challenge; standard chronic urticaria treatment regimens with antihistamines were used with modest improvement in case report series.1-4 Omalizumab is a recombinant humanized, monoclonal anti-IgE antibody that binds specifically to circulating Ig-E molecules and has been approved for the treatment of asthma. However, recent studies suggest that omalizumab might play an important role in the treatment of other potentially Ig-E mediated disease such as atopic dermatitis and there is currently lots of data showing effective results of omalizumab in the management of chronic urticaria.5-10 EAACI GA2LEN EDF WAO management of urticaria guideline recommend the use of omalizumab for fourth level therapy. 11 Here we present a case with chronic bullous urticaria who was unresponsive to high dose antihistamines and glucocorticosteroids responded very well to omalizumab therapy. A 76 year old man presented with large erythematous wheals on the different sites of the body. The wheals persisted up to one week and bullous lesions frequently formed on the surface of the wheals. He reported a 4 year history of spontaneous erythematous bullous wheals as well as recurrent attacks. Attacks were recurring every 2 weeks. He had no angioedema. He was receiving angiotensin-convertingenzyme inhibitors because of hypertension. There were many erythematous, edematous plaques with bulla formation on his back and abdomen which healed with crust formation (Fig. 1, 2). Dermographism was not seen. Laboratory findings included normal values for complete blood count with differential, comprehensive metabolic panel including antinuclear antibody, thyroid stimulating hormone level, C4 level, C 1 inhibitor function and concentration. Total IgE level was 57 kU L. Autologous serum skin test was positive. To verify the clinical diagnosis we performed a skin biopsy. Histological examination showed dermal edema with a perivascular mixed infiltrate, consisting of lymphocytes and eosinophils. Histopathological findings were also incuding loss of epidermis because of dermoepidermal separation with extravasated erythrocytes in dermis (Fig. 3). Direct immunofluorescent study was performed to rule out bullous pemphigoid that resulted with nonspecific findings. His signs and symptoms did not improve during administration of different non-sedating H1antihistamines, leukotrien antagonists or by increasing up to four-fold of the recommended dose. Emergency treatment with methyl prednisolone and short acting antihistamines did not provide a relief. He had hospitalisations every two weeks. He had no allergy related disease. After high dose corticosteroid therapy (1 mg kg methyl prednisolone) partial regression was seen. He felt more depressed because of the major reduction in his quality of life. Because of the patient’s unresponsive lesions to any treatment, 300 mg of omalizumab every 4weeks was administered subcutaneously after obtaining written informed consent. His last episode of bullous lesions was seen 1 week before initiation of therapy and he remained free of urticaria during 1 year of omalizumab therapy. He had no longer developed any urticarial symptoms and he had no need of any urticaria treatment. Bullous urticaria is a rare entity and it should be differentiated from bullous pemphigoid, bullous mastocytosis, insect bite reactions and contact dermatitis. Our patient has been in follow up for two years for recurrent urticaria and two biopsy specimens has been taken showing dermal oedema with eosinophil infiltration. Mastocytosis is characterised by mast cell infiltration in the dermis and bullous pemphigoid is characterised by IgG deposition on the basement membrane in direct immunofluorescent studies. We ruled out mastocytosis by histopathological examination and bullous pemphigoid by direct immunofluorescent study in our patient. Insect bite reactions and contact dermatitis are also ruled out by the history. The underlying mechanism of bullous urticaria is still unclear. There are cases of bullous delayed pressure urticaria which report that it is characterized by dermal infiltration of activated eosinophils within the lymphocytes.3,4 Bullous urticaria is considered as an IgE mediated eosinophilic disorder. Therefore omalizumab may be effective in this group of urticaria by binding free IgE and thereby by reducing free IgE in the serum. The reduction in functional IgE leads to a more than 95% down regulation of the IgE receptor.6 This is seen in mast cells, basophils and dendritic cells, and decreased antigen processing also results in less antigen presentation to Th2 cells which leads to less stimulation of eosinophils by cytokines. As eosinophils are shown predominant cells in bullous urticaria, omalizumab could decrease the eosinophil accumulation in dermis and can suppress inflammation by this mechanism. Histamine is known as a selective chemoattractant for eosinophils and pro-inflammatory responses is derived from the histamine-induced activation of eosinoAllergology International. 2014;63:495-497

Recognizing Pinch Purpura As The First Manifestation Of AL Amyloidosis

A 74-year-old female presented with a 6-month history of easy bruising as manifested by purpura after minor trauma to her face. Her physical examination was unremarkable except for the presence of pinch purpura scattered on her face (Figure 1). Laboratory tests showed leukocytes of 8100/μL, hemoglobin of 11.2 g/dL, platelets of 208,000/μL, prothrombin time of 11 s (normal range: 11.2-13.0 s), activated partial thromboplastin time of 25 s (normal range: 23.0-33.0 s), and erythrocyte sedimentation rate of 72 mm/h. Upon further workup, the presence of IgG lambda monoclonal gammopathy of the serum and lambda monoclonal light chain was found in urine immunofixation electrophoresis. Bone marrow biopsy revealed 7% lambda-restricted plasma cell infiltration, showing green birefringence with Congo red stain and vascular amyloid P deposition (Figure 2). There were no CRAB symptoms, organ dysfunction, or organomegaly. Echocardiography and pro-Btype natriuretic peptide results were normal. A diagnosis of amyloid light-chain (AL) amyloidosis initially presenting with purpura was made and a chemotherapy regimen of bortezomib and dexamethasone was started. Complete remission was achieved after six courses of chemotherapy and the purpuric lesions disappeared.

Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG)

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

Rituximab desensitization in three patients with severe rituximab allergy

Rituximab is a chimeric monoclonal antibody that targets CD20 positive B cells and has a positive effect on both overall and progression-free survival in B-cell lymphoid malignancies. Combination rituximab with chemotherapy treatment provide survival improvement. Although rituximab is an important treatment option in hematological malignancies, the risk of allergic reactions is high. These reactions are usually IgE-mediated and can be varied in regard of severity from urticaria to anaphylaxis. It is an option to interrupt the treatment and ommit rituximab therapy who had allergic reactions. Drug desensitization is another option and successful results have been reported by applying desensitization to such reactions. Drug desensitization alters the immune response to induce a state of temporary clinical tolerance to the allergic drug by giving gradual increasing of doses of drug at fixed time intervals. Herein, we present 3 cases successfully treated with rituximab desensitization. The cases were using rituximab with the diagnosis of Burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, respectively. Two cases had grade 2 and 1 case had grade 3 systemic allergic reaction with rituximab. There was no known allergy history in all 3 cases. All patients tolerated the desensitization protocol. The subsequent treatments of the patients were also given by desensitization protocol. A total of 12 desensitizations were administered to 3 cases. No severe or life-threating reactions were observed in subsequent applications. To date applying desensitization protocols ensure rituximab treatment safely. Rituximab desensitization can be performed at trained allergy centers, and it may be an appropriate option for rituximab allergic patients.