Ridvan Ali

Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group.

The combination of melphalan–prednisone–thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan–prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n = 122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m2/d) and P (60 mg/m2/d) for 4 d every 6 wk (n = 62) or MP and thalidomide (100 mg/d) continuously (n = 60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease‐free (DFS) and overall survival (OS). Overall, MPT‐treated patients were younger (median 69 yr vs. 72 yr; P = 0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P = 0.057). After 4 cycles of treatment (n = 115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P = 0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow‐up (median OS 26.0 vs. 28.0 months, P = 0.655; DFS 21.0 vs. 14.0 months, P = 0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3–4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P = 0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n = 8, 14.0%) than in the MPT arm (n = 2, 3.4%; P = 0.053). Long‐term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P = 0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation. This study is registered at http://www.clinicaltrials.gov as #NCT00934154.

The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases.

BackgroundAlthough bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event.MethodsTo underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow.ResultsThe main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO).ConclusionOur series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors.

Maternal and fetal outcomes in pregnancy complicated with acute leukemia: a single institutional experience with 10 pregnancies at 16 years

The incidence of acute leukemia in pregnancy is low and the management of acute leukemia during pregnancy is difficult. We have observed a total of 10 pregnancies in 8 patients. Six of the patients had acute myeloblastic leukemia (AML) and two of them had acute lymphoblastic leukemia (ALL). Three of the pregnancies were diagnosed when the leukemia was in remission, six at the time of leukemia diagnosis and one at the time of leukemic relapse. Six of the pregnancies were found in first trimester, three in the second and one early in the third. Three pregnancies ended with spontaneous abortion, three with intrauterine death and three with medical termination. One of spontaneous abortions and one intrauterine death developed during combination chemotherapy (daunorubicin, cytarabine). Only 1 healthy baby survived from the 10 pregnancies and this child was the not exposed to chemotherapeutic agents. None of the cases had gynecologic and obstetric complications. Five of eight pregnant women with leukemia died because of the primary disease.

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.

Idiopathic thrombocytopenic purpura in pregnancy: a single institutional experience with maternal and neonatal outcomes

We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by preeclampsia, one by ablatio placentae, and one by intrauterine death. Seven mothers received corticosteroid treatment, four high-dose immunoglobulin therapies, and one underwent splenectomy in the second trimester of gestation. At the time of delivery six mothers had normal platelet counts and seven had low platelet counts. Nine deliveries were by vaginal route and four were by cesarean section. Eleven infants were born with normal platelet counts and one was thrombocytopenic at the time of delivery. No infant showed any clinical signs of hemorrhage and there were no neonatal complications. Two fetuses died; one of them because of ablatio placentae and the other was intrauterine dead. In conclusion, ITP in pregnancy requires the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, anesthesiologist, and neonatologist is essential.

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.

Investigation of GSTP1 (Ile105V al) Gene Polymorphism in Chronic Myeloid Leukaemia Patients

Abstract The factors leading to the development of Chronic Myeloid Leukemia (CML) are not fully known. Associations between polymorphisms for genes encoding Glutathione S-transferase (GST) enzymes involved in Phase II detoxification reactions and susceptibility to some cancers have been shown in several studies. The aim of the present study was to investigate the influence of the GSTP1 (IIe105Val) gene polymorphism on human susceptibility to CML. Seventy-one CML patients and 67 control subjects with no cancer history were enrolled in our study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the GSTP1 (lle105Val) gene polymorphism. Genotypes were determined according to the bands that formed in agarose gels via gel electrophoresis. Leukocytes in the CML patient group were significantly different from those in the control group (p=0.0001). The frequency of the GSTP1 Val allele was found to be 22% in CML patients and 31% in controls. However, no statistical variation was found to exist between controls and patients in terms of the GSTP1 Val allele frequency (p=0.199). The relationship between the GSTP1 (IIe105Val) gene polymorphism and CML is not fully understood. Our results provide no evidence of a relationship between the GSTP1 (IIe105Val) gene polymorphism and susceptibility to CML in Turkish patients. However, these findings should be confirmed in studies with larger sample sizes.

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

Treatment of advanced classic Kaposi's sarcoma with weekly low‐dose paclitaxel therapy

Treatment of advanced classic Kaposi’s sarcoma with weekly low-dose paclitaxel therapy Several reports have been published recently documenting the efficacy of paclitaxel monotherapy in human immunodeficiency virus (HIV)-associated and post-transplant Kaposi’s sarcoma (KS). The standard dosing and frequency of this therapy has not yet been established, however. We present here an interesting case of classic KS with gastrointestinal involvement and human herpesvirus-8 (HHV-8) positivity responding to weekly low-dose paclitaxel monotherapy, suggesting a tolerable and alternative regimen in the elderly. A 76-year-old woman presented with multiple reddish-blue plaques and nodules of 7 years’ duration distributed widely on the distal upper and lower extremities and face (Fig. 1). Oral examination revealed a reddish-blue plaque, 1.5 cm in size, on the hard palate. No lymphadenopathy or organomegaly was detected by systemic examination. The histopathologic examination of the punch biopsy specimen was compatible with KS (Fig. 2). The patient was HIV negative, but HHV-8 was found to be positive in blood on polymerase chain reaction (PCR) analysis. Systemic evaluation of the patient revealed anemia (hemoglobin, 7.3 g/dL) and occult blood testing was positive. In addition to chronic gastritis, endoscopic examination demonstrated two similar nodules on the descending part of the duodenum which were confirmed histopathologically as KS. Computed tomographic examination of the thorax and abdomen did not show any metastatic lesion or lymphadenopathy. As a result of gastrointestinal involvement and widespread distribution of the lesions, weekly low-dose paclitaxel chemotherapy (60 mg/m in 250 mL of normal saline solution) was initiated. Because of this drug’s marked allergenicity, the patient was premedicated by the infusion of 40 mg dexamethasone intravenously 30 min prior to the paclitaxel infusion. Ten courses were administered. After eight courses of therapy, all lesions, including those on the oral mucosa, had dramatically regressed. The side-effects observed during therapy were alopecia and granulocytopenia. The patient received a total of 10 injections of granulocyte-colony stimulating factor during therapy. She experienced myalgia once after the first course of therapy. At the end of 10 courses, the skin lesions had improved with postinflammatory hyperpigmentation (Fig. 3). Endoscopic examination revealed the disappearance of duodenal lesions. A punch biopsy from the hyperpigmented macules showed no residual disease except for a few ecstatic blood vessels. The patient has been followed up for 15 weeks with no recurrence. The disseminated skin lesions and presence of duodenal involvement in this case warranted the application of chemotherapy as the best approach. Systemic medications that are Food and Drug Administration (FDA) approved are liposomal doxorubicin, paclitaxel, and interferon-α. As a result of previous experience demonstrating its efficacy as a single agent in KS, paclitaxel was preferred. Paclitaxel exerts its antitumor effects by several mechanisms, most importantly by the polymerization of microtubules, inhibition of cell division, and induction of cell death, possibly by the down-regulation of bcl-2 expression. Paclitaxel was