Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination. [Journal Article]
- Int J Clin Exp Pathol 2014; 7(9):6386-90.
Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma.
- Predictors and outcomes of suspected heparin-induced thrombocytopenia in subarachnoid hemorrhage patients. [Journal Article]
- Interv Neurol 2014 Aug; 2(4):160-8.
Heparin-induced thrombocytopenia (HIT) is a dreaded complication of heparin-related products and correlates with a worse outcome in aneurysmal subarachnoid hemorrhage (SAH) patients.To study the risk factors and outcomes of SAH patients suspected of having HIT, confirmed as present or absent by the platelet factor 4 (PF4) antibody test.All patients with presumed aneurysmal, nontraumatic SAH and having undergone a PF4 test were identified through our research patient database. Charts, laboratory values and images were analyzed retrospectively.We identified 166 patients with SAH who were tested for HIT; 42 patients (25%) had a positive antibody test. There was no difference in platelet profiles or mean platelet nadirs of HIT+ and HIT- patients (147 ± 93 vs. 153 ± 86 ×10(9)/l, respectively). Univariate analysis identified gender, magnesium prophylaxis, Fisher group 3, clipping versus coiling, presence of angiographic vasospasm, number of vasospasm treatments, and day of HIT testing as potential risk factors associated with HIT. A multivariate analysis indicated that female gender (OR 8.2, 95% CI 2.0-33.2), greater number of vasospasm treatments (OR 1.5, 95% CI 1.2-2.0), later day of HIT testing (OR 1.2, 95% CI 1.1-1.3), and clipping (OR 5.0, 95% CI 1.42-10.0) were independently associated with HIT positivity. HIT+ patients showed more infarcts on CT, longer ICU and hospital stays and worse modified Rankin Scale scores on discharge.The presence of HIT in SAH has adverse consequences and is more likely in female patients who have undergone aneurysm clipping and require multiple endovascular vasospasm treatments.
- Plasma cell leukemia: A case series from South India with emphasis on rarer variants. [Journal Article]
- Indian J Med Paediatr Oncol 2014 Jul; 35(3):211-4.
Plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell dyscrasia. They occur de novo (primary) or as a late manifestation of multiple myeloma (secondary). Patients present with anemia, thrombocytopenia, renal failure, organomegaly and extramedullary manifestations. We are presenting this series as it is the second largest series from India (16) with 4 young cases (under 40 years of age), more number of female patients and two having 'hairy cell' morphology. It is recommended that techniques like immunophenotyping and protein electrophoresis be performed, whenever the morphology is not characteristic of plasma cells.
- Osteopetrosis mimicking juvenile myelomonocytic leukemia. [Journal Article]
- Pediatr Int 2014 Oct; 56(5):779-82.
A 5-month-old boy developed splenomegaly, anemia, thrombocytopenia with elevated white cells, monocytosis and immature granulocytes in the peripheral blood. Bone marrow showed dysplasia without blastosis. Increased colony-forming unit-granulocyte-macrophage was found in the peripheral blood, mimicking granulocyte-macrophage colony-stimulating factor hypersensitivity. These findings fulfilled the diagnosis criteria for juvenile myelomonocytic leukemia (JMML), but no mutations in the CBL, NRAS, KRAS, or PTPN11 genes were detected. In addition to these findings severe hypogammaglobulinemia and elevated alkaline phosphatase were present. Bone X-ray showed dense and radiopaque bones with a bone-in-bone appearance characteristic of infantile malignant osteopetrosis (IMO). Genetic mutation in T-cell, immune regulator 1 (TCIRG1) was identified, confirming the diagnosis of IMO. Careful differential diagnosis including osteopetrosis, is therefore recommended in patients with clinical features and hematologic findings consistent with JMML.
- A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer. [JOURNAL ARTICLE]
- Invest New Drugs 2014 Oct 22.
To determine the maximum tolerated dose (MTD) of the combination of linsitinib (OSI-906), a dual inhibitor of IGFR and IR tyrosine kinase activity, and everolimus as treatment for patients with refractory metastatic colorectal cancer (mCRC).Eligible adult patients with refractory mCRC, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate end-organ function received escalating doses of OSI-906 and everolimus in a 3 + 3 design. Treatment continued until disease progression or unacceptable toxicity, with response evaluations every 8 weeks.Eighteen patients with metastatic CRC were treated. There were no dose-limiting toxicities (DLTs) in the first dose level (DL, OSI-906 50 mg BID; everolimus 5 mg QD). At DL2 (OSI-906 100 mg BID; everolimus 10 mg QD, n =6), three patients had DLTs considered related to everolimus (grade 3 mucositis, 2; grade 3 thrombocytopenia, 1). An amendment introduced DL2a (OSI-906 100 mg BID; everolimus 5 mg QD, n =5); DLTs were seen in two patients (one patient each: grade 3 thrombocytopenia with bleeding; inability to receive 75 % of doses due to neutropenia/thrombocytopenia). DL1 was the MTD; a total of 7 patients were treated at this dose. Common adverse events across all DLs included grade 1/2 fatigue (50 %) and anorexia (50 %). There were no objective responses to treatment; median time of study treatment was 7.6 weeks (range: 3.9-53 weeks).The MTD of OSI-906 and everolimus was 50 mg BID and 5 mg QD, respectively. No indications of clinical activity were observed in refractory mCRC patients.
- [Tolerability and efficacy of regorafenib in patients with unresectable metastatic colorectal cancer]. [English Abstract, Journal Article]
- Gan To Kagaku Ryoho 2014 Oct; 41(10):1231-6.
Regorafenib is an orally administered multikinase inhibitor that was approved for the treatment of unresectable metastatic colorectal cancer in Japan last year, following an international phase 3 trial(CORRECT)that provided evidence of a survival benefit. However, some concerns remain about high odd ratios of specific adverse events.We examined the clinical records of 16 patients(age: 57-78 years)treated with regorafenib for metastatic colorectal cancer that had progressed after all standard therapies were administered. Patients received either 160 mg(standard dose)or 80 mg(reduced at the physician's discretion)of regorafenib orally once a day, for the first 3 weeks of each 4-week cycle. Predefined dose reduction(by 40 mg, once)and dose interruption were permitted to manage treatment-related toxic effects.The median duration of treatment was 6.5 weeks(interquartile ratio[IQR]: 3.8-21.8). Dose modifications were required in 87.5% of patients, resulting in a relative dose intensity of 48.8%. Adverse events of grade 3 or higher related to regorafenib were hand-foot skin reactions(44%), fatigue(13%), thrombocytopenia(13%), anorexia(6%), and hypertension( 6%), in addition to severe drug-induced liver injury in 1 patient. Disease control was achieved in 75.0%(95% confidence interval[CI]: 50.0-93.8)of patients, although no patient had a partial response. Progression-free survival(PFS) and overall survival(OS)were 9.0 weeks(8.5-9.5 weeks)and 26.6 weeks(5.0-48.1 weeks), respectively.The efficacy of regorafenib was confirmed in late-stage cases that were refractory to standard chemotherapies. Most adverse events were manageable, although treatment was discontinued permanently in some cases because of hand-foot skin reactions, fatigue, and liver injury. The duration of treatment was short, but disease control, OS, and PFS were similar to those found in the CORRECT trial.
- The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors. [JOURNAL ARTICLE]
- Oncotarget 2014 Apr 27.
BCR-ABL1-specific tyrosine kinase inhibitors prolong the life of patients with chronic myeloid leukemia (CML) but cannot completely eradicate CML progenitors. The BH3 mimetic, ABT-263, targets prosurvival BCL2 family members, and has activity against CML progenitors. However, the inhibitory effect of ABT-263 on BCL-XL, which mediates platelet survival, produces dose-limiting thrombocytopenia. A second-generation BH3 mimetic, ABT-199, has been developed to specifically bind BCL2 but not BCL-XL. We determined the activity of ABT-199 against CML cell lines, as well as primary CML and normal cord blood (NCB) progenitors. We find that BCL2 expression levels predict sensitivity to ABT-199 in CML and NCB progenitors, and that high NCB BCL2 levels may explain the reported hematologic toxicities in ABT-199-treated patients. Also, while single agent ABT-199 has modest activity against CML progenitors, when combined with imatinib, ABT-199 significantly enhances imatinib activity against CML progenitors at concentrations predicted to avoid hematologic toxicities.
- Copper deficiency with 20q deletion and a paroxysmal nocturnal haemoglobinuria clone presenting with bicytopenia. [Journal Article]
- Indian J Hematol Blood Transfus 2014 Sep; 30(Suppl 1):372-5.
Copper plays an essential role in numerous enzymatic reactions in the human body and hypocupremia manifests itself as cytopenias and/or neuropathy. Copper deficiency is also a mimic of dysplasia, and this may cause diagnostic difficulties with true myelodysplasia. In this case report, we present a patient with anaemia, thrombocytopenia and marginally decreased leucocyte count, who was found to have low copper levels. In addition, he had isolated 20q deletion and a small paroxysmal nocturnal haemoglobinuria clone, which have not been reported previously. His counts normalized after steroid therapy followed by copper supplementation. This case is presented to highlight the fact that copper deficiency may be present without the characteristic morphologic changes, and may be coexisting with other abnormalities.
- A Novel WASP Gene Mutation in a Chinese Boy with Wiskott-Aldrich Syndrome. [Journal Article]
- Indian J Hematol Blood Transfus 2014 Sep; 30(Suppl 1):353-5.
Wiskott-Aldrich syndrome (WAS) is a rare inherited X-linked recessive immunodeficiency disease characterized by eczema, thrombocytopenia, immune deficiency, and bloody diarrhea and is caused by WASP gene mutations. This study reports a case of WAS with a novel mutation. A newborn Chinese infant was admitted to the hospital because of intermittent bloody stools, recurrent infections, and persistent thrombocytopenia. Genetic analysis of the coding sequences and flanking splice sites of the WASP gene showed a novel WASP gene deletion mutation (1144delA) at exon 10. Family history showed that both his mother and aunt had a heterozygous genotype of the WASP gene. The infant died at the age of 4 months due to persistent thrombocytopenia and severe pneumonia. A novel WASP gene deletion (1144delA) at exon 10 was identified in a Chinese infant with WAS. This base deletion results in a frame-shift mutation of the gene for an early stop codon at amino acid 444.
- Diffuse large B cell lymphoma in wiskott-Aldrich syndrome: a case report and review of literature. [Journal Article]
- Indian J Hematol Blood Transfus 2014 Sep; 30(Suppl 1):309-13.
Wiskott-Aldrich syndrome (WAS) is an X linked rare primary immunodeficiency syndrome with an increased propensity for infection, autoimmunity and malignancy. Here we report a male child, who was diagnosed with WAS at 1 year of age following evaluation for symptomatic thrombocytopenia and eczematous skin lesions. He presented later with lymphadenopathy, which was consistent with diffuse large B cell lymphoma on histopathology. He received 6 cycles of R-CHOP chemotherapy for the same and is presently in remission after 6 months. We review the major publications of lymphoma in WAS and discuss the pathological findings, treatment and prognosis of lymphoma in WAS.