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Acute Lymphocytic Leukemia (acute + lymphocytic_leukemia)
Selected AbstractsAcute lymphocytic leukemia in adolescence with multiple osteolytic lesions and hypercalcemia mediated by lymphoblast-producing parathyroid hormone-related peptide: A case report and review of the literaturePEDIATRIC BLOOD & CANCER, Issue 3 2005Hidemi Shimonodan MD Abstract Background Osteopathy is one of the common initial symptoms of acute lymphocytic leukemia (ALL) in children and adolescents, but multiple osteolysis accompanied by hypercalcemia is rarely observed. Procedure We treated a 14-year-old female who had multiple osteolytic lesions and hypercalcemia at initial onset of ALL. In this case we examined some humoral factors, which are known to associate with hypercalcemia in malignancies. Results Parathyroid hormone-related peptide (PTHrP) was elevated in serum, and reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed that the lymphoblasts produced PTHrP directly. Other humoral factors related to hypercalcemia were not detected. ALL relapsed in the bone marrow 3 months after achieving complete remission, and hypercalcemia and elevation of serum PTHrP were also observed. A second remission could not be achieved and hypercalcemia continued. The patient received allogeneic bone marrow transplantation. The serum calcium level became normal after the conditioning therapy. Before engraftment, however, the patient died of infection. Conclusions The present case suggests that blast-producing PTHrP might be associated with multiple osteolytic lesions and hypercalcemia. PTHrP expressed in the lymphoblasts may, in itself, confer a survival advantage to lymphoblasts and contribute to the refractory nature of the disease. © 2005 Wiley-Liss, Inc. [source] Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudineEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2003Tetsuhiro Chiba Abstract: We report a 38-yr-old male with acute lymphocytic leukemia (ALL), whose serological tests for the hepatitis B virus (HBV) before transplantation showed a chronic carrier status, and a liver biopsy specimen revealed chronic liver injury because of HBV. The patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his sibling who was hepatitis B surface antibody (HBsAb) positive. He had received lamivudine treatment for the prophylaxis of HBV reactivation during cytotoxic chemotherapy, and lamivudine administration continued after transplantation. Successful engraftment was documented 3 wk after PBSCT, and clearance of the hepatitis B surface antigen (HBsAg) was observed 2 months after PBSCT. Liver function tests transiently showed a mild elevation of aminotransferases on day 25, although this returned to normal after the dose escalation of the immunosuppressive agent. We presume that the combination of adoptive immunity transfer by bone marrow transplantation (BMT) from an HBsAb-positive donor and antiviral drugs such as lamivudine is beneficial in clearing HBV in chronic carriers. [source] Overweight and obesity and incidence of leukemia: A meta-analysis of cohort studiesINTERNATIONAL JOURNAL OF CANCER, Issue 6 2008Susanna C. Larsson Abstract We conducted a meta-analysis to summarize the available evidence from cohort studies on the association between excess body weight and incidence of leukemia. Studies were identified by searching the MEDLINE and EMBASE databases (1966,July 2007) and by examining the references of retrieved articles. A random-effects model was used to combine the results from individual studies. We identified 9 cohort studies with data on body mass index (BMI) or obesity in relation to incidence of leukemia. Compared with nonoverweight individuals (BMI < 25 kg/m2), the summary relative risks (RRs) of leukemia were 1.14 [95% confidence interval (CI), 1.03,1.25] for overweight individuals (BMI 25,30 kg/m2) and 1.39 (95% CI, 1.25,1.54) for obese (BMI , 30 kg/m2) individuals. On a continuous scale, a 5 kg/m2 increase in BMI was associated with a 13% increased risk of leukemia (RR, 1.13; 95% CI, 1.07,1.19). In a meta-analysis of 4 studies reporting results on subtypes of leukemia, the summary RRs associated with obesity were 1.25 (95% CI, 1.11,1.41) for chronic lymphocytic leukemia, 1.65 (95% CI, 1.16,2.35) for acute lymphocytic leukemia, 1.52 (95% CI, 1.19,1.95) for acute myeloid leukemia and 1.26 (95% CI, 1.09,1.46) for chronic myeloid leukemia. This meta-analysis indicates that excess body weight is associated with an increased risk of developing leukemia. © 2007 Wiley-Liss, Inc. [source] Disseminated cutaneous Fusarium moniliforme infections in a leukemic childINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2007Ching-Chi Chi MD A 5-year-old boy had a 10-month remission of acute lymphocytic leukemia (ALL) after chemotherapy. Re-induction chemotherapy was performed for relapse of ALL. Thereafter, he suffered from an episode of neutropenic fever with pneumonia. One week following control of the condition with antibiotics, a 1 × 1-cm, red, painful nodule appeared on the left thigh, which was initially suspected to be Pseudomonas infection. Parenteral ceftazidime and amikacin were administered, but persistent high fever, mild cough, and a few painful erythematous papulonodules on the face and lower extremities appeared several days later (Fig. 1). These lesions increased insidiously in diameter up to 2,5 cm with central necrosis. Hemogram showed neutropenia with a shift to the left [white blood cell (WBC) count, 2.1 × 109/L; neutrophil count, 0.21 × 109/L]. A skin biopsy showed heavy growth of hyaline branching septate hyphae in the deep dermis and subcutis, together with fat necrosis (Fig. 2). Invasion of molds into vessels and sweat glands was also seen. A culture from a lesion yielded Fusarium moniliforme, but no fungi were isolated from blood specimens. Only mild infiltrations on bilateral lower lung fields were detected by chest roentgenography. The skin lesions gradually healed and the fever subsided 2 weeks after the initiation of therapy with amphotericin B 30 mg and itraconazole 200 mg daily. Figure 1. A few painful erythematous papulonodules appeared on the face and lower extremities Figure 2. Skin biopsy showed heavy growth of hyaline branching septate hyphae in the deep dermis and subcutis along with fat necrosis (hematoxylin and eosin, ×400) Meanwhile, relapse of leukemia was detected by hemogram showing atypical leukocytosis (WBC count of 24,400 × 109/L, with blast cells representing 78%). A course of chemotherapy with cytarabine, mitoxantrone, and VP-16 was prescribed, subsequently resulting in neutropenia (WBC count, < 0.1 × 109/L; neutrophil count, 0/L) and spiking fever. Although the aforementioned antifungal therapy was continued, the centers of the originally healed lesions turned dusky red, swollen, necrotic, and ulcerative. There were more than 10 such ecthymiform lesions. After administration for 22 days, itraconazole was discontinued because of no appreciable effects. Granulocyte colony-stimulating factor (G-CSF) salvage was used, and the neutropenia gradually subsided 20 days later. In addition, the ecthymiform lesions gradually resolved. Amphotericin B was discontinued 1 week following neutrophil recovery. The patient died of Acinetobacter baumannii and Stenotrophomonas maltophilia sepsis 8 months later. [source] Telomerase activity and telomere length in acute leukemia: correlations with disease progression, subtypes and overall survivalINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2010Y. WANG Summary The progressive shortening of telomeres and the activation of telomerase are considered to be one of the important mechanisms in cellular immortalization and disease progression. Bone marrow samples were collected from 148 patients with acute leukemia (AL). Based on the stage of the disease, patients were divided into the newly diagnosed group, the relapsed group and the complete remission (CR) group. telomerase activity (TA) was examined by PCR-ELISA, and telomere length (TL) was examined by Southern blot analyses. TA and TL were analyzed in relation to AL stage and subtype. Five-year survival was analyzed using Kaplan,Meier survival curve. TA in AL patients was higher than healthy individuals. TA level was the highest in the relapsed group, followed by the newly diagnosed group, and then the CR group. TA had no difference between acute nonlymphocytic leukemia (ANLL) group and acute lymphocytic leukemia (ALL) group. But TA in group of subtype M3 was lower than other subtypes of ANLL. TL in AL group was shorter than the control group. TL was the shortest in the relapsed group, followed by the newly diagnosed group, and finally the CR group. TL exhibited an inverse correlation with TA. The group of patients with high TA had a significantly poorer five-year-survival than that of low TA group. TA is elevated and TL is shortened in AL patients. There is a significant inverse correlation between TL and TA. Patients in late-stage disease had shorter TL and higher TA than those in early stages. The shortened TL and elevated TA correlated with disease progression and relapse, and they may serve as prognostic factors for AL patients with poor outcome. M3 subtype is special with relative lower TA and long-lasting survival than other subtypes. [source] Cellular stress triggers TEL nuclear export via two genetically separable pathwaysJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Caroline A. Hanson Abstract TEL (translocation ets leukemia, also known as ETV6) is a repressor of transcription that is disrupted by the t(12;21), which is the most frequent chromosomal translocation in pediatric acute lymphocytic leukemia. TEL is modified by SUMOylation, and the lysine (Lys 99) that is conjugated to SUMO is required for TEL nuclear export. In addition, TEL is phosphorylated by p38 kinase, which is activated by cellular stress. Induction of cellular stress reduced the ability of TEL to repress transcription in vitro, but the mechanistic basis of this phenomenon was unclear. In this study, we show that osmotic stress causes re-localization of TEL to the cytoplasm and that p38-mediated phosphorylation of TEL is sufficient for this re-localization. However, impairment of both SUMOylation of Lys 99 and p38-dependent phosphorylation of Ser 257 of TEL were required to impair the re-localization of TEL in response to cellular stress induced by high salt, identifying two separate nuclear export pathways. Thus, alteration of the cellular localization of TEL may be a part of the cellular stress response and re-localization of TEL to the cytoplasm is an important step in the regulation of TEL. J. Cell. Biochem. 104: 488,498, 2008. © 2007 Wiley-Liss, Inc. [source] Fatal HHV6 infection in an immunocompromised patient presenting with skin involvementJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2010Anjela Galan Infection with human herpesvirus-6 (HHV6) has a broad distribution in the human population, with a seroprevalence approaching 100% worldwide. Primary infection takes place during childhood, after which the virus remains latent mostly in lymphocytes and monocytes at various sites. Immunosuppression can result in viral reactivation, associated with clinical sequelae and even death. We report a case of a disseminated HHV6 infection in a 53-year-old patient, who was immunocompromised after allogeneic bone marrow transplant treatment for acute lymphocytic leukemia. Initially, he presented with a macular eruption of the skin, followed by involvement of other sites. Histopathologic analysis of skin biopsies revealed superficial perivascular large atypical mononuclear cells with intranuclear and intracytoplasmic inclusions. Most affected cells labeled with antibodies to CD3 and CD43 as lymphocytes, and some labeled with CD68 as macrophages. Polymerase chain reaction (PCR) studies of the blood, skin, liver, colon, cerebrospinal fluid and brain were positive for HHV6 virus. Additionally, the serologic titers for HHV6 were high. Viral particles were also detected by electron microscopy (EM) in the colon. Although rare, HHV6 virus may be an important pathogen in immunocompromised patients, and may present initially in the skin. Awareness of this infection is critical to diagnosis in acute settings. Galan A, McNiff JM, Nam Choi J and Lazova R. Fatal HHV6 infection in an immunocompromised patient presenting with skin involvement. [source] Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Paola Giordano In a group of newly diagnosed acute lymphocytic leukemia (ALL) children we evaluated a number of hemostatic and inflammatory markers at diagnosis and at different time points during chemotherapy for the remission induction to identify alterations in the plasma levels of prothrombotic markers before and during the course of chemotherapy. The following plasma markers were evaluated: thrombin-antithrombin complex (TAT), D-Dimer, plasminogen activator inhibitor 1 (PAI-1), antithrombin, fibrinogen, von Willebrand factor (VWF) antigen and high molecular weight VWF (HMW-VWF) multimers, P-selectin, tumor necrosis factor alpha (TNF-,), and interleukin 6 (IL-6). Plasma samples were collected at the following time points: at T0 (baseline) and T1 (+24 days of therapy), T2 (+36 days therapy), and T3 (+64 days therapy). The results show that, at diagnosis, ALL children presented with laboratory signs of increased thrombin generation and fibrin formation (i.e. high TAT and D-dimer levels), fibrinolysis inhibition (i.e. high PAI-1 level), endothelial activation (i.e., high HMW-VWF and soluble P-selectin levels) and inflammation (i.e. high TNF-alpha and IL-6 levels). After starting induction therapy, the thrombin generation markers and inflammatory cytokines significantly decreased. To the opposite, PAI-1 and P-selectin significantly increased, suggesting an insult by chemotherapy on the vascular endothelium. These effects were more evident during steroid administration. Symptomatic venous thromboembolism (VTE) episodes developed in two cases during induction therapy, which did not allow the evaluation of the predictive value for VTE of laboratory markers. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Treatment of Philadelphia-positive acute lymphocytic leukemia with tyrosine kinase inhibitors: What is the optimal regimen?,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010Amber Fullmer No abstract is available for this article. [source] Acute lymphocytic leukemia in adolescence with multiple osteolytic lesions and hypercalcemia mediated by lymphoblast-producing parathyroid hormone-related peptide: A case report and review of the literaturePEDIATRIC BLOOD & CANCER, Issue 3 2005Hidemi Shimonodan MD Abstract Background Osteopathy is one of the common initial symptoms of acute lymphocytic leukemia (ALL) in children and adolescents, but multiple osteolysis accompanied by hypercalcemia is rarely observed. Procedure We treated a 14-year-old female who had multiple osteolytic lesions and hypercalcemia at initial onset of ALL. In this case we examined some humoral factors, which are known to associate with hypercalcemia in malignancies. Results Parathyroid hormone-related peptide (PTHrP) was elevated in serum, and reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed that the lymphoblasts produced PTHrP directly. Other humoral factors related to hypercalcemia were not detected. ALL relapsed in the bone marrow 3 months after achieving complete remission, and hypercalcemia and elevation of serum PTHrP were also observed. A second remission could not be achieved and hypercalcemia continued. The patient received allogeneic bone marrow transplantation. The serum calcium level became normal after the conditioning therapy. Before engraftment, however, the patient died of infection. Conclusions The present case suggests that blast-producing PTHrP might be associated with multiple osteolytic lesions and hypercalcemia. PTHrP expressed in the lymphoblasts may, in itself, confer a survival advantage to lymphoblasts and contribute to the refractory nature of the disease. © 2005 Wiley-Liss, Inc. [source] Toxic Epidermal Necrolysis After the Use of High-Dose Cytosine ArabinosidePEDIATRIC DERMATOLOGY, Issue 1 2001Alp Özkan M.D. A 13-year-old girl with acute lymphocytic leukemia was treated according to the protocol of the BFM Group (BFM-95, HRG). On the fifth day after administration of a high dose of ARA-C (2 g/m2 intravenously every 12 hours), she developed bullous lesions on the hands and soles that disseminated, evolving to necrosis, sepsis, and death on the 22nd day. ARA-C is frequently associated with dermatologic toxicity, but this is only the second case of toxic epidermal necrolysis described in connection with this drug. [source] Successful high-dose methotrexate chemotherapy in a patient with acute lymphocytic leukemia who developed acute renal failure during the initial treatmentPEDIATRICS INTERNATIONAL, Issue 6 2007TAKESHI ISODA No abstract is available for this article. [source] Phase 1 study of INNO-406, a dual Abl/Lyn kinase inhibitor, in Philadelphia chromosome-positive leukemias after imatinib resistance or intoleranceCANCER, Issue 11 2010Hagop Kantarjian MD Abstract BACKGROUND: INNO-406, a dual v-abl Abelson murine leukemia viral oncogene homolog (Abl)/v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog (Lyn) tyrosine kinase inhibitor (TKI), has demonstrated specific Lyn kinase inhibitory activity with no or limited activity against other sarcoma (Src) family member kinases. Several breakpoint cluster region (Bcr)-Abl kinase domain mutations are sensitive to INNO-406 in vitro, including mutations that involve a phenylalanine-to-leucine or phenylalanine-to-valine substitution at codon 317 (F317L and F317V, respectively). In the current study, the authors evaluated the use of INNO-406 in patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL) after imatinib resistance or intolerance. METHODS: A dose-escalation study was conducted at a starting dose of oral INNO-406 30 mg once daily. Cohorts of at least 3 patients were treated at each dose level until the maximum tolerated dose (MTD) was reached. Twice-daily dosing also was evaluated. Therapy was allowed to continue for a maximum of 24 months. RESULTS: INNO-406 was administered to 56 patients with imatinib resistance (n = 40) or intolerance (n = 16). Other previous treatments included nilotinib (n = 20 patients), dasatinib (n = 26 patients), and dasatinib/nilotinib (n = 9 patients). Common mutations at the time of study entry included a tyrosine-to-histidine substitution at codon 253 (Y253H) (n = 6 patients), a glycine-to-glutamic acid substitution at codon 250 (G250E) (n = 4 patients), a threonine-to-isoleucine substitution at codon 315 (T315I) (n = 4 patients), and F317L (n = 3 patients). Of 31 patients with CML in chronic phase who received INNO-406, the major cytogenetic response rate was 19%. No responses were observed in patients who had CML in accelerated phase, CML in blastic phase, or Ph-positive ALL. The dose-limiting toxicities (DLTs) at an INNO-406 dose of 480 mg twice daily were liver function abnormalities and thrombocytopenia. CONCLUSIONS: INNO-406 had anti-CML efficacy in a heavily pretreated study population. On the basis of the classic determinations of both DLT and MTD, the recommended phase 2 dose of oral INNO-406 was 240 mg twice daily. Lower doses of INNO-406 may be equally effective and should be explored. 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