Atilla Ozkan

Tumor lysis syndrome as a contributory factor to the development of reversible posterior leukoencephalopathy

IntroductionReversible posterior leukoencephalopathy syndrome (RPLS) is a recently described clinical and radiological entity comprising headache, seizures, altered level of consciousness and visual disturbances in association with transient posterior cerebral white-matter abnormalities.MethodWe report a young woman with Burkitt’s lymphoma who developed RPLS after combined chemotherapy administered during the tumor lysis syndrome.ResultsThe symptoms in this patient fitted well with those of RPLS; they included abrupt alterations in mental status, seizures, headache, visual changes and characteristic neuroradiological findings. She was given further combination chemotherapy without any neurological complications, at which time she had already recovered from both RPLS and tumor lysis syndrome.ConclusionAlthough many etiological factors have been reported in the development of RPLS, the underlying mechanism is not yet well understood. With prompt and appropriate management, RPLS is usually reversible, and chemotherapy can be continued after complete recovery from RPLS. We suggest that tumor lysis syndrome should be considered as a contributory factor to the development of RPLS in patients for whom treatment with combined chemotherapy for hematological malignancies is planned.

Invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia

BackgroundAspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA) according to the criteria that are established by European Organization for the Research and Treatment of Cancer and Mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for Aspergillus spp., and findings of computed tomography) and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible.Case presentationWe report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin B and underwent surgical pulmonary resection. The operative course was uneventful.ConclusionThis report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.

Tuberculosis presenting as immune thrombocytopenic purpura.

BackgroundAlthough various hematologic abnormalities are seen in tuberculosis, immune thrombocytopenic purpura is a rare event.Case PresentationWe report a case of a 29 year-old male who was presented with immune thrombocytopenia-induced hemoptysis, macroscopic hematuria and generalized petechiae. The patient was found to have clinical, microbiological and radiological evidence of active pulmonary tuberculosis. The immune thrombocytopenic purpura was successfully treated with anti-tuberculous drugs combined with corticosteroids and high dose immune globulin therapy.ConclusionImmune thrombocytopenic purpura can be one of the hematological manifestations of tuberculosis which has a global prevalence with increasing incidence secondary to HIV infection.

Hairy cell leukemia presenting with Guillain-Barre syndrome.

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder, which mainly infiltrates the bone marrow and the spleen, resulting in peripheral cytopenias and splenomagaly [1]. Unusual complications including autoimmune phenomena have been described in HCL [2 – 4]. Of these, to the best of our knowledge, Guillain-Barre syndrome (GBS) was reported only in two cases so far [5,6]. Here, we describe a HCL patient who presented with GBS at the time of diagnosis. A 61-year-old previously healthy male was referred to our department complaining of weight loss, night sweats, and pain, weakness and parasthesia progressing from distal to proximal limb muscles for the last 3 weeks. There was no preceding history of viral illness or vaccination or any medication. His physical examination revealed pale appearance, hepatomegaly (3 cm) and splenomegaly (3 cm). Precise neurological examination demonstrated second motor neuron type tetraparesis prominent in the lower extremities (20% muscle strength in lower, 80% in the upper extremities) with hypoactive deep tendon reflexes and loss of vibration sense. Blood picture showed Hb 10.9 g/dl, MCV 96 fl, WBC 10.66 10 l with 44% lymphocytes, 37% hairy cells, 17% PNL, and 2% band leukocyte differentiation, and a platelet count of 2126 10 l. Erythrocyte sedimentation rate was elevated (130 mm/h). Biochemistry tests were normal except for alkaline phosphatase. Serum cobalamin level was found in normal limits. Cytomorphological examination of the bone marrow demonstrated a normocellular marrow with hairy cells infiltration. Flow cytometry of the bone marrow cells revealed positivity for CD19 (64%), CD20 (96.1%), CD11c (98.8%), CD25 (99.1%), CD22 (98.9%), and CD103 (29.3%) and negativity for CD23 (8.5%) and CD5 (3.4%). Histopathological examination of the bone marrow established the diagnosis of HCL (Figure 1). Then, the patient was referred to the Neurology department for consultation. Whole spine magnetic resonance imaging was normal. Lumbar puncture was performed. Protein content of cerebrospinal fluid (CSF) was 201 mg/dl and CSF was acellular. Electroneuromyography (ENMG) was consistent with sensorymotor demyelinating polyneuropathy. The patient was diagnosed as GBS with albuminocytologic dissociation of CSF and ENMG findings reflecting demyelination in both sensory and motor nerves. He was treated with

Efficacy of bortezomib in combination chemotherapy on secondary plasma cell leukemia

We read with great interest the article by Finnegan et al. [1] in a recent issue of Leukemia & Lymphoma, describing the results of primary plasma cell leukemia (PPCL) treated with bortezomib. We would like to describe and share our experience in a patient with secondary plasma cell leukemia (SPCL), who was successfully treated with a combination of one dose of bortezomib, doxorubicin and dexamethasone, and in whom complete remission was maintained with the administration of a single dose of bortezomib every 3 weeks. A 59-year-old man was diagnosed with IgAk multiple myeloma (MM), stage IA, in April 2001. The management decision was to perform autologous stem cell transplantation following three cycles of combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD), but he did not respond to the therapy, and autologous stem cell transplantation could not be performed because of an inadequate stem cell collection. Therefore, from April 2001 to September 2004, he received successive treatments with six cycles of VAD, thalidomide alone, thalidomide plus dexamethasone, and melphalan plus prednisone, respectively. But he did not achieve complete remission. His treatment was complicated with peripheral sensory neuropathy and deep venous thrombosis during the treatment with thalidomide, and he was found to be homozygous for factor V Leiden abnormality. Moreover, he needed treatment for two pneumonia episodes. In September 2004, he presented with fatigue, loss of appetite, and multiple purpuric spots. On physical examination, he had no lymphadenopathy or hepatosplenomegaly. The peripheral blood counts showed hemoglobin 8.14 g/dl; platelets 326 10/l; and white cells count 13.16 10/l. Peripheral blood smear revealed 91% plasma cells. Bone marrow aspirate and trephine biopsy showed 90% plasma cells and plasmablasts. Flow cytometry of the bone marrow aspirate revealed intense positivity for CD38 and intracytoplasmic CD79a. Cytogenetic analysis was normal. The biochemical tests were normal except for calcium (8 mg/dl), total protein (9 g/dl) and albumin (2 g/dl). b2-microglobulin level was 5706 mg/l. Serum protein electrophoresis and immunofixation studies revealed IgAk paraprotein. Upon establishing the diagnosis of SPCL and obtaining the patient’s informed consent, treatment with bortezomib (1.3 mg/m, bolus injection, Day 1), doxorubicin (9 mg/m cont. inf., Days 1 – 4) and dexamethasone (40 mg p.o., Days 1 – 4, 9 – 12, 17 – 20) was commenced. At the end of the first cycle, circulating plasma cells disappeared from peripheral blood. His hemoglobin level and platelet count increased, and he became transfusion-independent. At the end of the 3rd cycle, peripheral blood counts returned to normal with a normal differential, and the percentage of plasma cells in the bone marrow decreased from 90% to 10%. At the end of the 6th cycle, he was in complete remission which was demonstrated both by pathological and serological studies. Afterwards, bortezomib 1.3 mg/m and zolendronic acid 4 mg every 3 weeks were employed as maintenance treatment. In March 2006, 12

Extramedullary Plasmacytoma Involving the Abdominal Vessels and Pancreas

To the Editor: We read with great interest the article by Attwell and colleagues [1] in a recent issue of Digestive Diseases and Sciences that described a case of IgA multiple myeloma (MM) involving two unusual extramedullary sites: the porta hepatis and peritoneum. The involvement of abdominal vessels and pancreas by plasma cell neoplasms is very rare and usually diagnosed at autopsy [1–3]. We would like to describe and share our experience in a patient with known MM who developed plasmacytoma on the chest wall and in the abdomen involving the abdominal vessels and pancreas, without concurrent relapse of the disease, and to add some points concerning the treatment of extramedullary plasmacytomas (EMP). A 64-year-old-man was diagnosed to have stage II MM of the IgA(λ) subtype in 2001. He was given a chemotherapy regimen with six courses of melphalan and prednisolone and achieved a plateau phase. In 2002, at the sixth month of the

Acute myeloblastic leukaemia (AML-M1) presenting with prominent gingival hypertrophy

A 39-year-old previously healthy man was admitted to the hospital with a 2-wk history of fatigue, gingival haemorrhage and overgrowth. His physical examination revealed pale appearance and prominent gingival hypertrophy (Fig. 1, left). Laboratory findings are as follows: Hb 8.3 g/dL, WBC 14.7 · 10/L with 74% blasts and platelet counts 13.4 · 10/L. The May–Grünwald–Giemsa stained cytological smears of the bone marrow aspiration showed hypercellular bone marrow with 89% myeloblasts (right). Cytochemistry revealed positivity for myeloperoxidase but negativity for combined esterase. Flow cytometric studies of the bone marrow cells revealed positivity for CD7 (83%), CD11c (44.4%), CD13 (78.8%), CD15 (55.2%), CD33 (82%), CD34 (82%), CD45 (87.8%) and CD117 (81.5%) antigens, and negativity for CD14 (5.7%) antigen. CD56 expression was not studied. Cytogenetic analysis revealed a normal karyotype and fluorescence in situ hybridisation for 11q23 rearrangements was negative. The diagnosis of acute myeloblastic leukaemia with French-AmericanBritish (FAB) M1 subtype was made. Gingival hypertrophy is observed in acute myeloblastic leukaemia with a frequency of 3–5%, in which FAB M5 subtype (66.7%) is the most common followed by M4 (18.5%) and M1, M2 subtypes (3.7%) (1). Conflict of interest

Profuse erythema multiforme induced by chlorambucil

Dear Editor, Purine analogs replaced alkylating agents as the standard first-line agents for chronic lymphocytic leukemia (CLL); however, chlorambucil is still being used in some of selected patients, particularly who are not candidates for more aggressive therapies due to poor performance status or co-morbid diseases. Although myelosuppression is being the most common toxicity of chlorambucil therapy, rare but serious complications such as allergic skin reactions may also occur. In this paper, we report a CLL patient who developed profuse erythema multiforme (EM) induced by chlorambucil. A 69-year-old woman had history of B cell CLL (Rai stage IV) diagnosis since 2002. She did not respond well to fludarabine therapy or to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). After four cycles of CHOP therapy, the patient developed severe pneumonia. Therefore, CHOP therapy was discontinued. Four months later, during off-therapy, she presented with night sweats, malaise, and progressively increasing white blood cell count (WBC). At that time, her physical examination revealed pale appearance, multiple palpable lymph nodes, splenomegaly (13 cm), and hepatomegaly (5 cm). Peripheral blood picture showed: Hb 9.5 g/dl, WBC 125×10/l, and a platelet count of 58×10/l. Chlorambucil at a dose of 8 mg/day was commenced. Two weeks later, she was admitted to the hospital complaining of skin eruptions for the last 10 days. There was no preceding history of viral illness or vaccination. Her history revealed that the skin eruptions developed on the fourth day of chlorambucil therapy, which was then discontinued. On physical examination, several target lesions with a central blister and surrounding purplish dark erythema on the face, trunk, and extremities were observed (Fig. 1). Histopathological evaluation of lesions was compatible with EM. Blood cultures for bacteria were negative. Prednisone (1.5 mg/kg/day) was commenced promptly. However, 8 days later, she died due to development of pneumonia before the resolution of her skin lesions. EM is an acute, self-limited skin disease characterized by the abrupt onset of symmetrical fixed red papules, some of which evolve into target lesions [1]. EM may occur in patients of all ages, particularly in adolescents and young adults [2]. Although many precipitating factors have been defined in EM, viral and bacterial infections and medicaments are the usual culprits. Nonetheless, chlorambucilassociated allergic skin reactions are very rare [3, 4]. Autoimmune disorders are well-known complications of CLL that may be observed either at presentation or during the course of the disease [5]. However, it is most likely that our patient has developed EM induced by chlorambucil, as: Ann Hematol (2007) 86:539–540 DOI 10.1007/s00277-007-0273-y

Superior vena cava syndrome: Initial presentation of acute myeloid leukemia (AML-M0) with near-tetraploidy+/TdT+/CD7+/CD34+/HLA-DR+

carcinoma patient with lung metastases in whom FDG PET showed increased uptake in the metastatic foci but not in the primary lesion. In conclusion, FDG PET results in our case suggest that FDG PET can clearly identify skeletal involvement. Also, FDG PET can detect some extraskeletal lesions such as muscle involvement and retro-ocular lesions. The role of FDG PET imaging in evaluation of extra-osseous lesions needs further investigation.