Supplementary Fig. S1 from A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells

Supplementary Fig. S3 from A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells

Supplementary Fig. S2 from A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells

AIMS:To study the toxicity of ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide) and modified-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in intermediate-risk and high-risk Hodgkin lymphoma patients.METHODS:High-risk patients received 4 cycles of modified-BEACOPP (m-BEACOPP) plus 4 cycles of ABVD. Intermediate-risk patients received 4 cycles of ABVE-PC plus 2 cycles of ABVD.RESULTS:From 2010 to 2014, 17 patients received 66 cycles of m-BEACOPP and 9 patients received 40 cycles of ABVE-PC. In the m-BEACOPP and ABVE-PC courses, respectively, significant thrombocytopenia (<50,000/mm(3)) occurred in 10.6% vs 0% of courses; anemia (Hb. <8 gm/dl) in 27.3% vs 15%; neutropenia (ANC<500/mm(3)) in 46.9% vs 32.5%; and febrile neutropenia in 33.3% vs. 22.5%. Only episode of documented infection (hepatic abscess) occurred in ABVE-PC. There were no episodes of sepsis, typhlitis or pneumonia in either group. All 26 patients are in remission with a median follow-up of 35 months (range, 17-61); and there have been no relapses. Two of 26 (7.7%) patients failed to achieve rapid early response after 2 cycles and complete remission after 4 cycles of chemotherapy; both achieved remission with more intensive regimens followed by radiation. The remaining 24 patients did not receive radiation therapy.CONCLUSIONS:Both m-BEACOPP and ABVE-PC regimens have acceptable toxicity; and thus can be used in most centres with optimum supportive care facilities. They offer promising response rate and relapse free survival without the need for radiation therapy in most patients; and thus may be considered for children with high-risk and intermediate-risk Hodgkin lymphoma.

OBJECTIVE:To define the efficacy and safety of low-dose rasburicase in children from south India with hematologic malignancies.METHODS:This study is a retrospective analysis of data on 41 children with hematologic malignacies with laboratory evidence of tumor lysis syndrome (TLS) or clinical features indicating high risk for developing TLS. Patients were treated with rasburicase in doses of 0.1-0.15 mg/kg dose, repeated when necessary.RESULTS:Male : Female ratio was 32:9. Thirty-six children had laboratory evidence of TLS and 5 were at risk for TLS. Diagnoses were T-cell acute lymphoblastic leukemia (ALL), 19; Pre-B ALL, 17; B-non-Hodgkin lymphoma (NHL), 2; T-NHL, 2; and acute myeloid leukemia (AML), 1. Initial plasma uric acid (PUA): median, 8.5 mg/dl (range, 4.3 to 45.5). Six had creatinine levels of >2 mg/dl on admission; and 10 had peak PO4 levels of >10 mg/dl. Dose of rasburicase used: median, 0.12 mg/kg (range, 0.08-0.24). Median reduction of PUA at 6 h: 80 % (range 40 to 98 %). Twenty-seven needed only one dose; 12 needed 2 or 3 doses; and two needed 5 doses each. One child required dialysis. None of the children developed anaphylaxis or hemolysis and there were no deaths from TLS.CONCLUSIONS:Low-dose rasburicase (0.1-0.15 mg/kg) is safe and effective in reducing PUA in Indian children with lymphoid malignancies, and thus it may reduce the risk of renal failure from TLS.

OBJECTIVES:To investigate the advantages and disadvantages of Totally implantable venous access devices (TIVAD) catheter in pediatric age group and also to review this subject in the recent literature and compare the results with the present results.METHODS:A total of 61 cases, 2 mo to 14 y old, were included in the index study. TIVADs were implanted in these patients for chemotherapy. The device was inserted under general anesthesia (GA) by open technique. All the children were followed up for a mean period of 7.2 mo.RESULTS:Out of 61 cases, 9 cases had complications; 3 requiring removal of the port due to infection and in one case the device had to be reinserted due to malpositioning, one had late wound dehiscence with exposed port chamber which needed operative correction and four had minor wound infections. There was no mortality. Complications like hemo or pneumothorax, arterial puncture, hematoma formation were very less with open technique of insertion of the port. Most patients and their parents were satisfied with TIVAD.CONCLUSIONS:Thus, TIVAD can be a useful device for many chronic patients who need an IV access for multiple injections especially in pediatric age group.

Inflammatory pseudotumors, now more aptly termed inflammatory myofibroblastic tumors (IMTs), are uncommon benign neoplasms, which have been reported in most organs and tissues in the body. Originally described and commonly found in the lung, they are also found in the liver of children and adults. We review the literature and analyze the features of the hepatic IMTs reported in children, along with a case report of a 15-month-old boy who had a persistent IMT in the liver and underwent surgical resection for the same following a trial of conservative management.

To describe the clinical features, treatment and prognosis of acquired thrombotic thrombocytopenic purpura (TTP) in children based on a single institution experience.

A 16-year old Caucasian girl was evaluated for scoliosis 9 years after bone marrow transplant (BMT) and 13 years after her initial ALL diagnosis. A chest radiograph showed a lesion of the right third rib. Histopathology was consistent with a high-grade OS. She died 5 months after OS diagnosis. There is no family history of cancer. Prior therapy comprised BFM standard risk for de novo ALL, St. Jude Children’s Research Hospital regimen and cranial-spinal radiation for central nervous system (CNS) recurrence, Children’s Cancer Group (CCG) 1941, and matched unrelated allo-transplant (conditioned with TBI and thiotepa, cyclophosphamide, and ATG) for bone marrow recurrence. Two years after transplant GH therapy commenced. A 15-year-old Hispanic girl with RAPADILINO syndrome experienced left lower extremity pain. Magnetic resonance imaging (MRI) showed a destructive lesion and biopsy was consistent with OS. At 11 years of age short stature was diagnosed. Growth hormone therapy was started and discontinued once OS was diagnosed. There is no family history of cancer. The Childhood Cancer Survivor Study reported the 25-year follow-up among survivors of childhood ALL. The cumulative incidence of SMN of 5.2% (6.2% for those receiving radiation therapy) at 25 years from diagnosis [2]. St. Jude Children’s Research Hospital (SJCRH) investigators reported the incidence of SMN as a first event in 2169 patients treated between 1962 and 1998 [3]. The cumulative incidence of SMN was 4.17% at 15 years and 10.85% at 30 years. Two cases of OS constituting 1.2% of SMN were observed.

The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia.

Our patient first developed thrombotic thrombocytopenic purpura (TTP) at age 10 years with an initial platelet count of 10,000/microL. She achieved remission with plasmapheresis (PE), but suffered 2 relapses in the next 2 years, each approximately 1 year from PE, with ADAMTS13 levels of <5%. Early in her third remission, with vincristine (weekly x 4 doses) and prednisone (for 2 weeks) her ADAMTS13 increased to 99% in 24 weeks, but decreased to <4% in the next 38 weeks. After 4 weekly doses of rituximab (375 mg/m(2)), her ADAMTS13 level reached 101% in 9 weeks and has remained consistently above 97% on bimonthly monitoring for more than a year. She remains in continuous clinical and hematologic remission with an ADAMTS13 level of 108% at 60 weeks from rituximab therapy and 124 weeks from her second relapse. This case report suggests that monitoring ADAMTS13 level at regular intervals in recurrent TTP may help us identify patients at risk for further relapse; and such a relapse may be prevented, or at least delayed with timely rituximab therapy, thus reducing morbidity from relapsed TTP and its treatment.