Murat Ozbalak

Azacitidine has limited activity in ‘real life’ patients with MDS and AML: a single centre experience

Myelodysplastic syndrome (MDS) represents a heterogeneous group of potentially malignant diseases of bone‐marrow stem cells. Acute myelogenous leukaemia (AML) is an inevitable outcome for many patients with MDS. Azacitidine has been reported to result in comparably higher response rates and improved survival than other treatment strategies. In this retrospective study, we report the results on 25 ‘real life’ patients with MDS, CMML or AML treated with azacitidine between 2005 and 2009. All patients fulfilled the World Health Organization criteria for MDS and AML. No eligibility criteria other than diagnosis were considered. Complete response (CR) rate was observed in three of the 25 ‘real life’ patients (12%) with a median duration of CR of 5 months (4–6 months). Seven patients (28%) had mono‐ or bi‐lineage haematologic improvement and 15 patients (60%) showed neither morphologic nor haematologic response. Among 17 non‐AML patients, the median time from onset of Aza‐C treatment to AML transformation was 10 months (4–15 months). Overall death rate was 72%. All of the eight AML patients died. The death rate under Aza‐C among non‐AML patients was 59%. Unlike the results of the clinical trials, our data show that Aza‐C has a limited activity in ‘real‐life’ patients with MDS and AML. It is obvious that Aza‐C can induce complete or partial responses in a considerable number of MDS patients but responses are usually not durable as we observed in our patients. Copyright

Severe Bone Marrow Failure Due to Valganciclovir Overdose After Renal Transplantation From Cadaveric Donors: Four Consecutive Cases

Valganciclovir is an l-valyl ester pro-drug of ganciclovir that was initially used to treat cytomegalovirus (CMV)-associated retinitis in patients with human immunodeficiency virus. Currently, it is also indicated for the prevention of CMV disease in solid-organ transplantation. It is primarily eliminated via the kidneys through glomerular filtration and tubular secretion. Decreased renal function results in decreased drug clearance. Valganciclovir has been reported to cause usually mild to moderate hematologic adverse effects such as leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia. Severe and fatal bone marrow depression has been described in 1 adult patient. Herein, we describe the cases of 4 patients with end-stage renal disease who underwent cadaveric renal transplantation and received valganciclovir prophylaxis for CMV at a standard dose of 900 mg/d despite persistant renal failure. This therapy resulted in severe bone marrow failure after 18 to 20 days in all 4 patients, with fatal infections in 2 patients. This report demonstrates the in vivo pharmacodynamics of valganciclovir overdose in terms of hematotoxicity in the setting of renal impairment. Valganciclovir, as its derivative ganciclovir, should be used cautiously in patients with renal impairment.

Is valganciclovir really effective in primary effusion lymphoma: case report of an HIV(−) EBV(−) HHV8(+) patient

Primary effusion lymphoma (PEL) is a human herpesvirus 8 (HHV8) associated lymphoproliferative disease characterized by effusions in body cavities, and lack of tumor mass. Valganciclovir is a treatment option in PEL, however, little is known about its clinical efficacy. Ganciclovir has been reported to be effective in HHV8(+) multicentric Castlemans disease (MCD) by decreasing the plasma HHV8 load, which is an important factor in the induction and persistence of MCD, Kaposis sarcoma (KS), and PEL. But there is no information about the efficacy of valganciclovir on HHV8 associated lymphoproliferative diseases. Here, we present the first EBV and HIV negative, HHV8 positive PEL case treated with valganciclovir; for whom it initially reduced the viral load leading to a transient partial improvement in the clinical status, but failed to induce a complete and durable remission.

Detailed Analysis of Diffuse Large B Cell Lymphoma Patients: A Single-Center, Retrospective Study

The aim of this single-center, retrospective study was to investigate the impact of rituximab, reconsider the validity of International Prognostic Index (IPI), and evaluate the prognostic role of the cell of origin (CoO) in a relatively young cohort. Three hundred twelve diffuse large B cell lymphoma patients (median age: 52) were included. Rituximab significantly improved the 3- and 5-year progression free survival (PFS) (70% versus 65% and 41% versus 36%, resp.; P < 0.001) but led only to a slight, insignificant increase in 3- and 5-year overall survival (OS) (71% versus 77.3% and %67 versus 74.5%, resp.; P = 0.264). In the young, low risk patient subgroup (aaIPI = 0&1; n = 129), rituximab improved 3- and 5-year PFS and OS rates (P < 0.001 and P = 0.048, resp.). The efficacy of rituximab in young high risk patients was comparable to the literature. CoO data were available in 190 patients. The OS at 3 years was 79% for GC and 64% for non-GC subgroups (P = 0.014). To the best of our knowledge, this is the first study which investigated the impact of R-CHOP in the context of CoO and IPI in a relatively young cohort. CoO was not an independent risk factor for prognosis in the multivariate analysis although patients with GC showed a significant survival advantage in the univariate analysis. CoO was also found to be a significant determinant of response in refractory/relapsed patients. Our results confirm the efficacy of rituximab in low and high risk, young patients outside of a randomized clinical trial setting.

An Unusual Presentation of a Chronic Lymphocytic Leukemia Patient with 17p Deletion After Reduced-Intensity Transplantation: Richter Syndrome and Concomitant Graft-Versus-Host Disease—Case Report

Chronic lymphocytic leukemia (CLL) patients with 17p deletion comprise a challenging subgroup associated with poor overall survival. These patients should be treated with alternative strategies. Reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) can achieve long-term remission in this ultra-high-risk CLL group. Herein, we described a CLL patient with 17p deletion who developed Richter syndrome with extranodal involvement of the liver soon after RIC allo-SCT despite apparent acute graft-versus-host disease. The majority of chronic lymphocytic leukemia (CLL) patients respond well to chemoimmunotherapy. Patients who show ultra-high-risk genetics, such as 17p deletions, comprise a challenging subgroup of patients with poor response to chemoimmunotherapy and median life expectancy <2-3 years at the time of first-line treatment. Current treatment approaches for patients with 17p deletion include agents acting independently from the DNA damage pathway, such as alemtuzumab and high-dose corticosteroids. RIC allo-SCT for consolidation can achieve long-term remission in this ultra-high-risk CLL group.(1,2) Richter syndrome (RS) represents the clinicopathologic transformation of CLL to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL).(3) RS appearing after allo-SCT can be managed by tapering of immunosuppression, followed by dose-escalated donor lymphocyte infusion titrated to the degree of leukemia response and graft-versus-host disease (GVHD) encountered.(4) Herein, we describe a CLL patient with 17p deletion who developed RS with extranodal involvement of the liver soon after RIC allo-SCT despite apparent acute GVHD (aGVHD).

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.

Inflammatory myofibroblastic tumor mimicking a relapse in a patient with Hodgkin's lymphoma: report of an unusual case and review of the literature

New PET‐positive lesions in previously treated patients with lymphomatous malignancies need further investigations. Relapse, sarcoidosis and secondary malignancies are the most important differential diagnosis. Inflammatory myofibroblastic tumors (IMT) is a rare complication after treatment of Hodgkins disease and every PET‐positive lesion should be biopsied to prevent unnecessary intervention.

Bronchus Associated Lymphoid Tissue Lymphoma Presenting with Immunodeficiency and Multiple Pulmonary Nodules

Bronchus Associated Lymphoid Tissue Lymphoma (BALTOMA) is a rare subgroup of pulmonary non-Hodgkins lymphomas (NHLs) comprising less than 1% of all cases. It constitutes 3.6% of all extranodal lymphomas and only 0.5–1% of primary pulmonary malignancies. They are usually low grade B-cell lymphomas and are considered to originate from the mucosa associated lymphoid tissue (MALT) of the bronchi. Here, we represent a rare case of BALTOMA presenting with immunodeficiency and multiple pulmonary nodules.