Clinical and electrophysiological evaluation of patients with thalidomide-induced neuropathy.

BACKGROUND: Whether thalidomide induces a sensory ganglionopathy or a length-dependent axonal neuropathy is disputed. Moreover no agreement exists concerning the effects of thalidomide dosage on the clinical and electrophysiological findings. OBJECTIVE: We examined the effect of age, gender disease duration, total cumulative dose on the clinical and electrophysiologic parameters. METHODS: Fifteen patients who had previously received 100 mg/day of thalidomide for the treatment of multiple myeloma were evaluated retrospectively. Clinical findings and nerve conductions studies were evaluated using a modified total neuropathy scoring system. RESULTS: Sensory symptoms (p = 0.033, r = 0.552) and objective sensory findings (p = 0.002, r = 0.730) worsened with higher thalidomide doses. There was no effect of age, gender and disease duration, neither on clinical symptoms and objective findings, nor on electrophysiologic data. Twelve patients (80%) developed the electrophysiological findings of neuropathy. Six (40%) had pure sensory and 4 (26.6%) had sensori-motor peripheral neuropathy, while 4 (26.6%) had carpal tunnel syndrome. Sural sensory nerve action potential (SNAP) amplitudes were more prominently reduced compared to SNAPs obtained from the upper extremities. Sural SNAP amplitude showed a tendency toward reduction as the total cumulative dose, although it is not statistically significant (respectively; p = 0.187). Significantly reduced ulnar peroneal and tibial compound muscle action potential amplitudes, slow motor nerve conduction velocities of the ulnar and peroneal nerves were found in the study group compared to reference norms (p < 0.05). CONCLUSION: Our results suggest that thalidomide produces a dose dependent peripheral neuropathy, mainly localized to the peripheral nerves in a length dependent manner. The patient must be monitored closely to prevent irreversible consequences.

Evaluation of superoxide dismutase enzyme activity of polymorphonuclear leucocytes, erythrocytes and thrombocytes in patients with chronic myeloproliferative disorders.

This study aimed to investigate the activity of the antioxidant enzyme superoxide dismutase (SOD) in the three main cell types in chronic myeloproliferative disorders (CMPD) patients, i.e. polymorphonuclear leucocytes (PMNLs), erythrocytes and thrombocytes, prior to therapy. Patients with reactive neutrophilia (RN) and healthy volunteers were included as controls. The SOD activity of PMNLs was significantly decreased in CMPD and RN patients compared with healthy volunteers, whereas the SOD activity of erythrocytes was found to be significantly increased in patients with CMPD and RN compared with healthy volunteers. There were no significant differences in the SOD activity of thrombocytes between CMPD patients, RN patients or healthy volunteers. This study indicates that the activity of the SOD enzyme in two cell types is different in CMPD patients compared with healthy subjects. Thus, SOD activity may be altered dependent on cell type and due to specific cell function.

Cardiac systolic function in patients receiving hematopoetic stem cell transplantation: risk factors for posttransplantation cardiac toxicity.

One hundred eleven patients who received 125 hematopoetic stem cell transplantations (HSCT) with myeloablative conditioning regimens were retrospectively evaluated for the development of cardiac toxicity (CT). The aims of this study were to assess the frequency of cardiac complications in patients receiving HSCT and to investigate the value of pretransplantation variables to predict posttransplantation CT. Severe grade III-IV CT was not observed in this cohort, in whom pretransplantation eligibility criteria excluded the patients with a left ventricular ejection fraction (LVEF) of 50% or less. Grade I-II CT was seen in 13.4% patients. Patients with a history of previous mediastinal radiotherapy, high doses of anthracycyclines, and a longer interval between diagnosis and treatment were found to have higher risk of developing CT. Pretransplantation ferritin levels and the type of HSCT did not seem to have an effect on posttransplantation cardiac complications. Our results indicated that CT was managable in patients with a LVEF of at least 50%.

Treatment of sinusoidal obstruction syndrome with defibrotide: a single-center experience.

Sinusoidal obstruction syndrome (SOS) is a frequent, troubling, and potentially fatal complication of hematopoietic stem cell transplantation. Despite promising results with defibrotide (DF), no treatment has been established as standard. DF is a single-stranded polydeoxyribonucleotide, obtained from controlled depolymerization of porcine intestinal mucosal cells. It has antithrombotic, antiischemic, antiinflammatory, and thrombolytic properties without significant side effects. We retrospectively evaluated the charts of 80 consecutive patients, with 89 hematopoietic stem cell transplants for hematologic malignancies. The results of early initiation of DF treatment in 14 patients with SOS are presented in this study. Fourteen patients, 8 males and 6 females % median age 40.5 years (range, 16-46 years) were diagnosed to have SOS. Disease severity was classified as severe in 6 (42.85%), moderate in 4 (28.57%), and mild in 4 (28.57%) patients. We treated 14 patients with DF for a median of 21.5 days (range, 4-39 days). All 14 patients received DF after the diagnosis of SOS. Three patients with severe and all of the patients with mild to moderate SOS responded to treatment with complete resolution of SOS-related signs and symptoms. All patients responding to DF were alive at 100 days posttransplantation. There was no significant drug-related side effect among patients treated with DF. With an overall response rate of 78.56% and a 50% complete response rate in severe SOS cases and minimal side effects, we suggest that DF is the best available agent to treat SOS.

Arteriovenous shunting in patients with multiple myeloma and high-output failure.

UNLABELLED: High-output cardiac failure is one of the cardiovascular problems associated with multiple myeloma and frequently seen in patients with extensive bone lesions. The purpose of this study was to search arteriovenous shunting in patients with multiple myeloma and cardiac failure. METHODS: After the exclusion of other causes of congestive heart failure, 11 patients whose cardiac indices were higher than or equal to 4 liter/min/m2 were selected for the study (7 women, 4 men; mean age 59.64 +/- 8.92 yr). All patients had Stage II-III disease and femoral involvement in radiological examination. Arteriovenous shunting was determined by means of intra-arterial injection technique of 99mTc-macroaggregated albumin (MAA) particles. A quantitative analysis of all scans was performed, and the results were correlated with cardiac index. RESULTS: Mean cardiac index was 4.33 +/- 0.36 liter/min/m2 in the study group. In all cases, arteriovenous shunting was detected (18.70% +/- 17.29%), and inhomogenous, increased radioactivity accumulation was revealed in the femoral region (lesion-to-background ratio 2.71 +/- 2.08). This zone corresponded to the area of infiltration in a radiograph. A significant correlation was found between shunting values and cardiac indices (r = 0.7899, p = 0.004, Spearman). Although all patients had varying degrees of anemia, we did not find such a relationship between the degree of anemia and cardiac index. CONCLUSION: Arteriovenous shunting within involved skeleton contributes significantly to the development of high-output cardiac failure in multiple myeloma.

A randomized trial of assessment of efficacy of leukapheresis volumes, 8 liters vs 12 liters.

It is logical to expect that large-volume leukapheresis may be able to collect adequate numbers of PBSC with fewer procedures. To date, there is no agreement on the optimal volume of leukapheresis. Therefore, in this study we compared 8 l volume with 12 l and assessed whether a 50% increase in the blood volume processed would decrease the number of leukaphereses each patient needed to collect > or =2.5 x 10(6) CD34(+) cells/kg in normal mobilizers. PBSC mobilization was done with cyclophosphamide etoposide followed by rhG-CSF in all patients. Forty patients were randomized to undergo 8 l leukaphereses (n = 20 patients) or 12 l leukaphereses (n = 20). The median numbers of leukaphereses required in order to collect > or =2.5 x 10(6) CD34(+) cells/kg in patients processed with 8 l and 12 l were 1 (range 1-5) and 1 (1-4), respectively (P = 0.50). The median number of total nucleated cells (TNC) collected per patient was greater for the 12 l group (7.47 x 10(8)/kg vs 3.90 x 10(8)/kg, P < 0.001), as was the median number of total mononuclear cells (TMNC) (4.26 x 10(8)/kg vs 2.16 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+)cells collected per patient (8.94 x 10(6)/kg vs 8.60 x 10(6)/kg, P = 0.85). The TNCs and TMNCs collected per leukapheresis were again greater for the 12 l group (3.64 x 10(8)/kg vs 1.91 x 10(8)/kg, P = 0.001 and 2.17 x 10(8)/kg vs 0.88 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+) cells collected per leukapheresis (3.98 x 10(6)/kg vs 3.26 x 10(6)/kg, P = 0.90). This study showed that there is no difference between 8 l and 12 l volumes in regard to collected CD34(+) cells/kg and also the use of a 12 l leukapheresis volume did not decrease the number of leukaphereses performed compared with a 8 l leukapheresis volume. In fact, the use of the larger leukapheresis volume had the disadvantage of adding 60 min to the time the patient was on the machine.

Therapy-related refractory anemia with ringed sideroblasts in chronic lymphocytic leukemia. involvement of 3q21 region.

Therapy-related myelodysplastic syndrome/acute myelogenous leukemia (t-MDS/AML) is extremely rare in chronic lymphocytic leukemia (CLL) despite extensive use of alkylating agents. We present a case of heavily treated CLL with resultant therapy-related refractory anemia with ringed sideroblasts (RARS). A complex cytogenetic abnormality including involvement of 3q21 was detected and to our knowledge, is the first report of a RARS case with a 3q21 abnormality.

del(17)(q25) in a patient with hairy cell leukemia: a new clonal chromosome abnormality.

Clonal chromosomal aberrations are reported in about 25% of the patients with hairy cell leukemia (HCL). No consistent cytogenetic abnormality has been described in HCL; most of the chromosomal changes found have been deletions and inversions, with the rare occurrence of translocations. While most of the chromosomal aberrations in HCL are common to the ones found in B cell chronic lymphocytic leukemia and other B cell lymphoproliferative disorders, there are also certain chromosomal changes that are not found in other B cell lymphoproliferative disorders. We present here a 63-year-old male patient with hairy cell leukemia with the clonal del(17)(q25), which has not previously been reported in HCL.

Pars plana vitrectomy in chronic myelogenous leukemia with vitreous hemorrhage.

Pars plana vitrectomy operations were performed on two cases of vitreous hemorrhage due to chronic myelogenous leukemia. Fundus examination and fluorescein angiography revealed optic disc neovascularization in both, which is a rare fundus finding in chronic leukemias. The first case seen with vitreous hemorrhage in both eyes also had diabetes mellitus with a negative family history, and had received laser therapy on his right eye. His chronic myelogenous leukemia was diagnosed 4 months after vitrectomy was performed on this eye, when he presented with widespread subcutaneous hemorrhages. The second case showed a nonproliferative retinopathy with old laser scars in his right eye and vitreous hemorrhage in his left eye, and had no diabetes mellitus. The diagnosis of chronic myelogenous leukemia was made before the vitrectomy operation when the physical examination revealed splenomegaly. The pathogenesis of retinal and optic disc neovascularization in myeloproliferative diseases, its possible relation with chemotherapy, and the results of the vitrectomy operations were discussed with special emphasis on the importance of ruling out chronic leukemias and other blood dyscrasias in vitreal hemorrhages, retinopathies of unknown origin, and even in diabetic retinopathies with a negative family history.

Hemoglobin Lepore Boston in a Turkish Family.

An abnormal hemoglobin was detected in a Balkan immigrant Turkish family. Erythrocyte morphology was similar to ß-thalassemia trait. Molecular analysis showed that the abnormal hemoglobin was Hemoglobin LeporeBoston. All affected family members were in heterozygote state and asymptomatic.

Impact of Fluorescence in Situ Hybridization in the Detection of Cryptic Fusion Transcript PML/RARA and A Complex t(5;15;17) in a Case of Acute Promyelocytic Leukemia.

Genetic aspects of a 28 year-old female patient with typical morphological and clinical features of acute promyelocytic leukemia is presented. Pml/rara fusion transcript and a complex translocation involving chromosomes 5, 15 and 17 were detected by fluorescence in situ hybridization (FISH) technique which was applied as in adjunct to conventional cytogenetics. The patient deceased soon in spite of the immediate ATRA and cytostatic therapy.

Prophylactic use of fluconazole in neutropenic cancer patients.

This study was carried out on 70 patients with haematological or solid malignancies who were receiving chemotherapy and/or radiotherapy. Forty-one patients were randomly assigned to receive fluconazole, 400 mg/day, while they were neutropenic. Systemic fungal infection developed in four of the 41 patients (9%) receiving prophylaxis in comparison to nine of 29 patients (31%) not receiving prophylaxis. The incidence of systemic fungal infection was significantly different between the groups receiving prophylaxis and those not receiving it (p < 0.05). Fluconazole was found to be effective for preventing systemic fungal infections in neutropenic patients with cancer.

Mobilization of peripheral blood stem cells with chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation of different doses of rhG-CSF.

To date, no randomized study has compared different doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG-CSF following mobilization chemotherapy on yields of CD34+ peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n = 25) versus 16 microg/kg/d (n = 25) of rhG-CSF following mobilization chemotherapy. The median number of CD34+ cells collected after 8 microg/kg/d of rhG-CSF was 2.36 x 10(6)/kg (range, 0.21-7.80), compared with 7.99 (2.76-14.89) after 16 microg/kg/d (P < 0.001). Twenty out of 25 (80%) patients in the low-dose and 23 out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 microg/kg and 16 microg/kg of rhG-CSF were 12 (10-20) and 9 (8-11) respectively (P < 0.001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P = 0.10), number of red blood cell (P = 0.56) and platelet transfusions (P = 0.22), days of total parenteral nutrition requirement (P = 0.84), fever (P = 0.93) and antibiotics (P = 0.77), and number of different antibiotics used (P = 0.58). These data showed that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy were associated with a clear dose-response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 microg/kg/d was as effective as 16 microg/kg/d except for a rapid neutrophil engraftment in the high-dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG-CSF, lower doses may be used for PBSC collections following chemotherapy-based mobilization regimens in this cost-conscious era.