Clofarabine in Acute Myeloid Leukemia. the Spanish Experience

Abstract Abstract 4279 Introduction: Clofarabine (CLF) is a purine nucleoside analog approved by FDA and EMA in refractory pediatric ALL patients. Phase I and II studies have reported Clofarabine activity in AML. Aims: To evaluate the experience in Spain with (CLF) in the treatment of adult AML patients, analyzing effectiveness and toxicity profile. Method: This is a multicenter retrospective study including AML patients treated in Spain with CLF by compassionate use. Main points were complete remission as IWRv2003 criteria and toxicity as CTCAE v3.0 of NCI scale. Result: Between July 2007 ans April 2011 a total of 76 AML patients were treated with CLF based chemotherapy in Spain. We obtained clinical data from 64 cases. Median age at CLF treatment 52.4 years (18–77). Male/Female: 31/33. Previous Myelodisplastic syndrome 12 (18%). Cytogenetic data was available in 58 patients (90%), and 28 of them had high-risk cytogenetic. CLF treatment: 56 patients received CLF as salvage therapy (23 in AML relapse and 33 in refractory disease), median previous lines 2 (0–7), were the remaining 8 patients were untreated patients. CLF was administered in combination with AraC in 94% patients and the 91% received a five days schedule. The most frequents CLF dose/day were: 40 mg/m2/day in 39 patients, 30 mg/m2/day in 11 patients, and 20 mg/m2/day in 9 patients. Response and outcome: Nineteen (35.8%) patients achieved complete remission and 64.1% had resistant disease. Mean survival time 14.3 ± 1.4 months. The statistical analysis shows a significant difference in the CR rate between first line therapy (CR 82%) and savage therapy in relapsed (CR 45%) and salvage therapy in refractory (CR 18%), (p0.012). Neither adverse cytogenetics nor previous MDS did influence CR. (p0.57 and p0.53 respectively). Toxicity: All patients presented grade IV hematological toxicity with grade IV neuthopenia, grade IV trombopenia and transfusion depend anemia. The incidence of extra hematological toxic effects were low, creatinine >3 mg/dL: 4 cases (6%); bilirrubine > 3mg/dL: 9 cases (14%). Eleven (17%) patients died during Induction. Conclusions(opcion1): The revised experience in Spain with CLF as compassionate used in AML confirms the effectiveness of Clofarabine as a salvage regimen. Of note was that CLF could potentially overcome some adverse known factors as cytogenetics. Disclosures: Off Label Use: Clofarabine in AML is an off-label use.

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Novel Strategies to Treat Children with Refractory or Relapsed Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v126.23.4927.4927 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4927-4927

Author(s):

Luca Lo Nigro ◽

Emanuela Cannata ◽

Piera Samperi ◽

Silvana Munda ◽

Daria Bottino ◽

...

Keyword(s):

Flow Cytometry ◽

Complete Remission ◽

Imatinib Mesylate ◽

Salvage Therapy ◽

Unrelated Donor ◽

Induction Phase ◽

Off Label Use ◽

Chromosome 11 ◽

Off Label ◽

Label Use

Abstract Background AML is an aggressive disease. Current pediatric protocols ensure a 60% survival rate (Pession A et al, Blood 2013), reaching a plateau of intensiveness. Nevertheless, patients with primary induction failure (PIF) (10%) or relapse (30%) after stem cell transplantation (SCT) still have a very poor outcome. Novel therapeutic strategies are needed. Case 1. In January 2013, a 13 year-old female with FAB-M1-AML, presenting with chromosome 11 monosomy, was enrolled on AIEOP-AML-2002/01 protocol (Pession A et al, Blood 2013) and showed a PIF after two cycles of induction phase. Leukemic blasts arose in a low peripheral blood cell (PBC) count, even in response to second line treatment (I-BFM-AML-relapse2001 protocol). A third line experimental therapy, azacitidine (AZA) and rapamycin, failed to induce remission. Low PBC count with blasts still remained. Based on a bright expression of CD117/cKit, detected by flow cytometry, we designed a salvage therapy with AZA (75mg/mq/day for 7 days, every 21 days), in association with Imatinib Mesylate (375 mg/mq/day). We observed an increase of PBC count, with rapid disappearance of blasts. After two courses of AZA-Imatinib, the patient achieved complete remission. Subsequently she underwent SCT from an unrelated donor (UD) (Nov/2013). Nine months later, immune-suppressive therapy was withdrawn and we confirmed complete remission with a 100% donor engraftment. She is currently alive and in remission. Case 2. In October 2013, a 13 year-old male with FAB-M5-AML, presenting with a complex karyotype and specific molecular markers (FLT3-ITD and NSD1-NUP98), was enrolled on AIEOP-AML-2002/01 protocol. He achieved complete remission after induction phase. Nearby SCT-UD program, he presented colonization with two multi-resistant-gram-negative bacteria. For this reason, he was shifted to a haplo-identical SCT program. He received two haplo-SCT from his mother (April/2014) and his father (June/2014) respectively, after which he showed a bone marrow relapse (Sept/2014). Based on his low performance status, we designed a salvage therapy with cytosine arabinoside (100 mg/day i.v. in a total 8-days/cycle) Sorafenib (600 mg/day orally, already started before the first haplo-SCT), in association with PEG-Asparaginase (Oncaspar) at 3500 UI/i.v. weekly for 4 administrations. Surprisingly we observed an increasing signs of cutaneous grade II graft-versus-host-disease (GVHD), confirmed by flow cytometry analysis (high T-cell suppressors/NK cells), consistently with an increasing rate of donor's DNA (Dec/2014). Therefore, after a second cycle, the patient achieved the complete remission (Jan/2015) and a third haplo-SCT (Feb/2015) was given, using NK-alloreactive donor cells from his mother. Currently, the patient is alive and in complete remission with 100% donor. Conclusion. Our experience suggests that innovative combinational therapies are able to rescue patients with PIF or relapsed AML after SCT, the worst candidates. Association of a tyrosine kinase inhibitor with a demethylating agent showed a synergistic effect on leukemic blasts. More interestingly, PEG-LASP combined an anti-leukemic effect to an immune-modulation on donor's lymphocytes, as shown by immunophenotypic analyses. Disclosures Off Label Use: We used Imatinib Mesylate and PEG-L-Asparaginase in two children with AML: an off-label use for indication and age. .

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Prevalence of methylphenidate use by Master of Medicine students at a South African university

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2021-140991 ◽

2021 ◽

pp. postgradmedj-2021-140991

Author(s):

Willem Andries Nienaber Louw ◽

Ryan Alroy Davids

Keyword(s):

South African ◽

Undergraduate Students ◽

Performance Enhancement ◽

Off Label Use ◽

Undergraduate Medical Students ◽

Online Questionnaire ◽

Cross Sectional ◽

Off Label ◽

Significant Difference ◽

Label Use

BackgroundMethylphenidate is mainly used for the treatment of attention-deficit/hyperactive-disorder (ADHD). Its effect of increased attentiveness leads to the potential of off-label use by students for academic enhancement—previously demonstrated in undergraduate students. No publication exists on postgraduate student use of methylphenidate.ObjectivesTo provide a summary of the self-reported prevalence and correlates of methylphenidate use in Masters of Medicine (MMed) students registered at the Faculty of Medical and Health Sciences of a South African university.MethodsA cross-sectional study was conducted. Data were collected via a self-administered anonymous online questionnaire distributed by email to 505 registered MMed students.ResultsOf the 253 responses (response rate 50.1%) received 71 (28.1%) have used methylphenidate. Only 2.4% have been diagnosed with ADHD. The majority (73.2%) obtained it without a formal medical consultation. Self-prescription (26.8%) and prescription by a colleague without consultation (23.9%) contributed significantly. Academic performance enhancement was the primary motivation for use in 71.8% and 42.3% of users started using methylphenidate while registered as an MMed student. There was no statistically significant difference in terms of gender (p=0.151), age (p=0.288) or year of study (p=0.149).ConclusionsOff-label use of methylphenidate is prevalent in MMed students registered at this South African university. The prevalence is significantly higher than in undergraduate medical students. The non-conventional means of access is of great concern. Efforts should be made to discourage self-prescription, educate students on the dangers of methylphenidate use, promote better access regulation and enhance psychological support.

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Therapeutic Strategy for Elderly Patients with ACUTE Myeloid Leukemia (AML) Carrying the DNMT3A Mutation

Blood ◽

10.1182/blood.v124.21.5269.5269 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5269-5269 ◽

Cited By ~ 1

Author(s):

Elena Rossetti ◽

Monica Crugnola ◽

Cecilia Caramatti ◽

Luisa Craviotto ◽

Elena Masselli ◽

...

Keyword(s):

Bone Marrow ◽

Septic Shock ◽

Complete Remission ◽

Elderly Patients ◽

Induction Chemotherapy ◽

Off Label Use ◽

Bone Marrow Blast ◽

Off Label ◽

Blast Count ◽

Label Use

Abstract BACKGROUND: AML in the elderly is associated with low complete remission (CR) rates after induction therapy, poor survival and high treatment-related mortality. 5-Azacytidine (5-AZA) has emerged as a valid substitute of the Conventional Care Regimens (CCR) in a small subset of patient with a bone marrow blast count ranging from 20% to 30%. However, in a off-label use, 5-AZA may also be used in patients with bone marrow blast infiltration >30%. Furthermore, 5-AZA can be also used for the maintenance therapy after the bone marrow blast count has been reduced under the 5% cut-off. AIMS: to assess both safety and efficacy of in-label use of 5-AZA in elderly AML patients who have reached a bone marrow blast count between 5% and 30% after an induction conventional chemotherapy. METHODS: from 2010 to 2013, 13 patients (8 males; 5 females) with a median age of 74 (range 64-86) years and a newly diagnosed AML have been enrolled. At the diagnosis, the median bone marrow blast count was 45% (range 24%-95%). Cytogenetics showed: normal karyotype in 7 patients, chromosome 8 trisomy in 2, complex karyotype in 4. A DNMT3A mutation was documented in 5 cases. Neither FLT3-ITD mutations nor NPM1 mutations were present. According to age, performance status and comorbidities, all patients received a CCR induction chemotherapy. Low Dose Cytarabine, 100mg/sqm, was given subcutaneously for 5 days in 4 patients, Fludarabine (25mg/sqm intravenously for 5 days) and Cytarabine (2gr/m2 intravenously for 5 days) in 4 and the ICE schedule- Idarubicine (10mg/sqm intravenously for 3 days), Cytarabine (100mg/sqm intravenously for 5 days) and Etoposide (50mg/sqm intravenously for 3 days) in 5. At the day +31 bone marrow evaluation, no one obtained a Complete Remission, in 5 patients blast count ranged between 20% and 30%; in 4 between 15% and 20%; and in 4 between 5% and 10%. Then, all patients received 5-AZA at 75mg/sqm subcutaneously for 7 days every 28 days. The median number of cycles was 8 with a minimum of 1 cycle and a maximum of 15 cycles. Adverse hematological events were: grade III-IV neutropenia in 7 patients (54%) and thrombocytopenia in 9 patients (69%). Fever was the major non-hematological side effect during 5-AZA: fever was of unknown origin (FUO) in 4 patients, infection-related in 4 (2 pneumonias, 1 sepsis from Pseudomonas Aeruginosa and 1 from KPC). One patient died after the first cycle for septic shock due to KPC. RESULTS: Among the 12 evaluable patients the median survival was 16 months (range 2 – 44). Our data showed a longer median survival (17 months) in the 5 patients with DNMT3A mutation in comparison with those with wild-type DNMT3A (11 months). In consideration of the limited number of patients, the p-value was 0.47. In addition, a reduction of transfusion requirements as well as an improvement of quality of life were obtained. Therapy with 5-AZA was overall well tolerated as only one patient needed a long-term hospitalization and died from septic shock. In conclusion, we showed that a bone marrow blast reduction after conventional induction chemotherapy and a subsequently treatment with 5-AZA can be a valid option in elderly patients with AML and DNMT3A mutation. More patients and longer follow-up are required for confirming these encouraging preliminary results. Disclosures Off Label Use: Gemtuzumab Ozogamicin in AML.

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Prognostic Impact of CD20 and CD25 Expression in Patients with Philadelphia-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL).

Blood ◽

10.1182/blood.v114.22.984.984 ◽

2009 ◽

Vol 114 (22) ◽

pp. 984-984 ◽

Cited By ~ 1

Author(s):

Fabio P.S. Santos ◽

Susan O'Brien ◽

Deborah A. Thomas ◽

Jorge Cortes ◽

Stefan Faderl ◽

...

Keyword(s):

Research Funding ◽

Adult Patients ◽

Lower Percentage ◽

Prognostic Impact ◽

Off Label Use ◽

Conventional Chemotherapy ◽

Off Label ◽

Cd25 Expression ◽

Significant Difference ◽

Label Use

Abstract Abstract 984 Poster Board I-6 Background: The Ph chromosome is the most common cytogenetic abnormality in adult patients with ALL and is associated with a higher risk of relapse and death. With the introduction of tyrosine kinase inhibitors (TKI; imatinib, dasatinib), the treatment of patients with Ph+ ALL has evolved. Regimens combining conventional chemotherapy with TKI have lead to significant improvements in the outcome of these patients. However, there is still a high incidence of relapse, and the determination of prognostic factors in these patients might lead to the development of risk-adapted therapy. CD20 is a cell surface marker expressed in 40% of adult patients with ALL, and it is associated with worse survival (Thomas D et al, Blood 2009; 113: 6330-6337). CD25 is the a-chain of the IL-2 receptor and has been reported to be associated with adverse outcomes in Ph+ ALL (Paietta E et al, Blood 2008; 112:Abstract 1500). Aims: To determine the prognostic impact of CD20 and CD25 expression in patients with Ph+ ALL. Methods: We retrospectively reviewed data of patients with Ph+ ALL treated at our institution with conventional chemotherapeutic protocols (Hyper-CVAD) alone or combined with TKI (Hyper-CVAD + imatinib and Hyper-CVAD + dasatinib). None of the patients received therapy with Rituximab. CD20 and CD25 expression were assessed by flow cytometry, and the cut-off for positivity was 20%. Survival was estimated by Kaplan-Meier method and compared by log-rank test. Results: We analyzed 126 patients with Ph+-ALL treated at our institution from November, 1992, until February, 2009. Patients received Hyper-CVAD alone (N=44), Hyper-CVAD + Imatinib (N=47) and Hyper-CVAD + Dasatinib (N=35). Median age of the whole cohort was 49 years (range 16-84). CD20 was positive in 69 of 124 (57%) evaluable patients. CD25 was positive in 63 of 112 (56%) evaluable patients. Patients that were CD20-positive had a higher incidence of peripheral lymphadenopathy (21% vs. 7%, p=0.04). Patients that were CD25-positive had lower lactate dehydrogenase (LDH) levels (median 1006 IU/L vs. 1433 IU/L; p=0.01), lower percentage of bone marrow blasts (median 86% vs. 90%, p=0.02), higher platelet counts (median 50×109/L vs. 32×109/L, p=0.01) and a higher incidence of CNS disease at diagnosis (21% vs. 4%, p=0.01). The complete response rate of the whole cohort was 91%. There was no impact of CD20 or CD25 positivity on disease-free survival (DFS) and overall survival (OS) of patients treated with Hyper-CVAD alone. In patients treated with Hyper-CVAD + dasatinib, CD20 positivity was associated with improved DFS (Figure 1) (median – not reached [NR] vs. 48 weeks [wks], p=0.01) and OS (median NR vs. 65 wks, p=0.06). Patients treated with Hyper-CVAD + imatinib who were CD20-positive had better DFS (median 91 vs. 57 wks, p=0.77) and OS (median 118 vs. 73 wks, p=0.98), but this did not reach statistical significance. There was a trend for worse survival in patients treated with Hyper-CVAD + dasatinib that were CD25 positive, but without a statistically significant difference (median DFS 55 wks vs. NR, p=0.10; median OS 85 wks vs. NR, p=0.11). We repeated the analysis combining Hyper-CVAD + dasatinib and Hyper-CVAD + imatinib (Hyper-CVAD + TKI). There was no significant difference in DFS and OS by CD20 expression (median DFS 130 wks vs. 53 wks, p=0.11; median OS 124 wks vs. 74 wks, p=0.11) or CD25 expression (median DFS 63 wks vs. 86 wks, p=0.33; median OS 100 wks vs. 117 wks, p=0.39). Conclusion: In patients with Ph+-ALL treated with regimens combining conventional chemotherapy and TKI, expression of CD20 may be associated with better survival outcomes. CD25 did not influence survival in our patients. More studies are needed to better determine the prognostic value of these markers and implement risk-adapted strategies treatment. Disclosures: Off Label Use: Off label use of imatinib and dasatinib in combination with cytotoxic chemotherapy. Cortes:Novartis: Research Funding; Bristol Myers Squibb: Research Funding. Kantarjian:Novartis: Research Funding; Bristol Myers Squibb: Research Funding.

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Allogeneic Hematopoietic Cell Transplantation in AML: Comparable Results After Matched or Mismatched Unrelated Versus Matched Related Transplantation.

Blood ◽

10.1182/blood.v114.22.1199.1199 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1199-1199 ◽

Cited By ~ 1

Author(s):

Birgit Federmann ◽

Christoph Faul ◽

Wichard Vogel ◽

Lothar Kanz ◽

Wolfgang Andreas Bethge

Keyword(s):

Overall Survival ◽

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Unrelated Donor ◽

Off Label Use ◽

Hematopoietic Stem ◽

Off Label ◽

Significant Difference ◽

Label Use

Abstract Abstract 1199 Poster Board I-221 Currently, most treatment algorithms reserve the use of allogeneic hematopoietic stem cell transplantation (HCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR) to patients with a matched related donor (MRD) and intermediate/high-risk disease. However, the role of HCT from a matched or mismatched unrelated donor (MUD/MMUD) in patients with AML remains to be defined. We retrospectively analyzed a cohort of 219 consecutive adult patients (98 female, 121 male) with AML who received HCT from 2000-2009 at our institution. The patients were transplanted after either myeloablative (MAC, n=139) or dose-reduced-conditioning regimens (RIC, n=80). Median age of patients was 50 years (range, 18-76). 77 patients were transplanted from MRD, 80 patients from MUD and 62 patients from MMUD (one antigen mismatch (MM)=31; two antigen MM=2; one allel MM=24; two allel MM=3, one antigen/one allel MM= 2). In all but six patients receiving MMUD grafts, ATG was included in the conditioning. Age, risk profile and pretreatment were evenly distributed among the three cohorts of patients. At time of HCT 22 (MRD), 18 (MUD) and 28 (MMUD) patients were not in CR. Current overall survival is 40 of 77 (52%) in patients transplanted from MRD, 48 of 80 (60%) from MUD and 34 of 62 (55%) from MMUD with a median follow-up of 1309 (range, 98-3173), 796 (range, 87-3075) and 648 (range, 111-1973) days of alive patients, respectively. Kaplan-Meier-estimated 3-year overall survival (OS) was similar with 54% after MRD-, 56% after MUD- and 46% after MMUD-HCT (p=0.4554). In patients transplanted in CR, 3-year estimated OS was also comparable (64% MRD vs. 58% MUD vs. 55% MMUD, p=0.6614). However, in patients transplanted in partial remission (PR) we observed a trend for a better survival in patients receiving a MUD graft (30% MRD vs. 46% MUD vs. 39% MMUD, p=0.1707). In the patients receiving MAC we observed a better OS compared to RIC with an estimated 3-year OS of 58% vs. 38% (p=0.1047) mainly due to a lower incidence of relapse. In the subgroup of patients receiving MRD-HCT this survival benefit was significant (61% vs. 21%, p= 0.0327) while there was only a trend for MUD- or MMUD-HCT (60% vs 45%, p=0.5702 and 49% vs. 43%, p= 0.7566, respectively). There was no significant difference in the incidence of acute GvHD >II with 25% (MRD), 35% (MUD) and 34% (MMUD) or chronic GvHD with 43% (MRD), 46% (MUD) and 34% (MMUD), respectively. A significant better survival of patients with limited cGvHD vs. extensive or without cGvHD (estimated 3-year OS 73% vs. 34% vs. 47%, p=0.0001) was observed. This advantage was present in all subgroups with a significant better survival in the group with MRD (86% vs. 38% p= 0.0034), a trend in MUD (67% vs. 55% p= 0.0564) and MMUD (59% vs. 55%, p= 0.3111). No significant influence on survival or GVHD of the degree and loci of HLA-mismatch could be detected. In conclusion in our cohort of patients, HCT from MUD or MMUD in AML resulted in a similar outcome compared to MRD. In patients with PR at time of HCT, the use of MUD and occurrence of limited cGVHD may lead to improved survival due to an enhanced graft-versus-leukemia-effect. Disclosures: Off Label Use: some chemotherapeutical agents in the conditioning are off-label-use.

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Protein Expression Clusters Can Differentiate Leukemia Subtypes in Pediatric Leukemia

Blood ◽

10.1182/blood.v124.21.3784.3784 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3784-3784

Author(s):

Terzah M Horton ◽

Yihua Qiu ◽

Gaye Jenkins ◽

Steven M. Kornblau

Keyword(s):

Protein Expression ◽

Expression Profiles ◽

Off Label Use ◽

Protein Activation ◽

Off Label ◽

Protein Clusters ◽

Significant Difference ◽

Pediatric All ◽

Protein Expression Profiles ◽

Label Use

Abstract Background Although AML and ALL are thought to arise from different progenitor cells, (common myeloid vs. common lymphoid) they share many clinical features and pathophysiological characteristics, such as excessive proliferation in association with blocks in differentiation, that raise the question of whether they might share mechanistic commonalities despite separate ontologic origins. This in turn would suggest common therapies to utilize in cases with similar mechanisms of action. Using reverse-phase protein lysate arrays (RPPA), we strove to determine if RPPA could 1) determine protein activation differences between pediatric ALL and AML, and 2) determine if protein expression clusters were affected by sample collection method, an issue critical to assessing protein activation pathways in the setting of cooperative group clinical trials. Methods We generated a custom RPPA with 132 leukemia enriched samples. The array included 59 AML (3 APL, 1 TMD, 1 relapse) and 73 ALL (58 pre-B, 15 T-ALL, 6 relapsed) patients. Median age was 9.1 years (range 0.0 – 22.1 years). Samples were enriched for leukemia cells using ficoll followed by magnetic bead separation, either CD3/CD19 depletion (AML), or B/T-cell isolation (ALL). The RPPA was probed with 194 strictly validated antibodies (139 antibodies assessing total protein expression, 36 phosphoproteins, 6 cleaved forms, and 3 methylation sites). Samples were collected in either heparin tubes (n=101) or CellSave preservations tubes (Veridex) (n=97), with 57 samples having both tube types. Results Clustering demonstrated that AML and ALL have highly different protein expression and activation patterns. Pre-treatment samples collected in Cell Save preservation tubes revealed two protein clusters dividing the patients into two groups based on the levels of 62/194 significantly differentially expressed proteins (p=0.01, FDR = 0.027). An AML-dominant cluster contained 31 AML and 4 ALL among its 35 members. The ALL-dominant cluster had 62 ALL and a lone AML sample among 63 members. Using heparin tubes, four protein clusters were observed which divided patients into three clusters based on the differential expression of 83 proteins (p=0.01, FDR<0.023). The ALL-dominant cluster, composed of 53 members, had 51 ALL and 2 AML samples. The two AML patients in the ALL group included a patient with difficult to treat AML that achieved CR after 3 cycles of standard AML therapy with the proteasome inhibitor bortezomib, and a patient with 11q23 ALL that subsequently underwent a lineage switch to AML. There were two AML clusters, one with 85% AML (middle cluster in figure) with 17 AML and 3 ALL and the other with 27 patents (far left cluster) consisting of 70% AML (18 AML and 1 TMD) along with 8 ALL samples. In the far left cluster, of the 8 ALL cases, 5 had changes involving chromosome 21, including four with t(12;21), and 1 with trisomy 21. ALL samples in total had only 8/73 with the t(12;21) translocation, indicating a statistically significant difference (p=0.002, two-tailed Fisher's exact test). Twenty-seven proteins were different in both the CellSave (CS) and heparin analyses. An additional 34 proteins, mostly epigenetic modifiers and apoptosis pathway proteins (Bcl2, BAD, BAX), were seen in the CS samples. An additional 52 proteins were detected in the heparin group, many related to cell stress pathways. Conclusion Protein expression profiles strongly divided pediatric ALL from AML. Since this classification scheme is dependent on protein expression and functional activation states, it may be possible to further identify patients with different risk characteristics based on protein expression profiles. However, at least 111 of 194 proteins showed similar expression in both AML and ALL suggesting that there may be commonalities in mechanisms shared between leukemias of different lineages. Further analysis of protein functional groups and pathway utilization are in progress to define both differences and commonalities. Figure 1 Figure 1. Disclosures Off Label Use: bortezomib: off label use in pediatric AML as part of a COG clinical trial.

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Multicenter Postmarketing Surveillance of Ondansetron Therapy in Pediatric Patienrs

Annals of Pharmacotherapy ◽

10.1177/106002809402800116 ◽

1994 ◽

Vol 28 (1) ◽

pp. 85-92 ◽

Cited By ~ 16

Author(s):

Kellie D. McQueen ◽

Jerrod D. Milton

Keyword(s):

Adverse Reactions ◽

Prescribing Patterns ◽

Off Label Use ◽

Free Standing ◽

Children's Hospitals ◽

Off Label ◽

Children’S Hospitals ◽

Significant Difference ◽

Hospital Patients ◽

Label Use

OBJECTIVE: To identify prescribing patterns of ondansetron, to provide a general overview of the therapeutic responses and possible adverse effects to ondansetron in selected children's hospitals, and to evaluate this methodology of surveillance and assess its effectiveness as a means to collect postmarketing experience with a drug in pediatric patients. DESIGN: This survey examined the use of ondansetron in 210 children. Complete drug and medical histories, indications, doses, possible ondansetron-associated adverse reactions, and daily responses to ondansetron therapy were recorded by a study pharmacist for each patient. Patients were followed until discharged from the clinic or hospital and/or until ondansetron therapy was discontinued. SETTING: The survey was conducted in seven free-standing children's hospitals across the US. Hospitals ranged in size from 100 to 331 beds (average 234). One hospital was located on the West coast, one on the East coast, one in the Rocky Mountain region, one in the Southwest region, and three in the Midwest. PARTICIPANTS: The selection of study participants was limited to member free-standing children's hospitals of the Pediatric Pharmacy Administrative Group. Selection was based on geographic location and availability of a pharmacist to coordinate the study. One pharmacist at each study site served as surveillance coordinator. Each pharmacist monitored without intervention the use of ondansetron in 30 children. Patients were enrolled consecutively from physicians' orders for ondansetron. Enrollment was open to clinic and hospital patients. Patients were excluded if more than 48 hours of retrospective review was required. MAIN OUTCOME MEASURES: The survey queried patient demographics, type of antineoplastic therapy administered, indications and dosing regimen(s) for ondansetron, additional antiemetic agents administered, and clinical response. Adverse drug reactions and prescriptions for ondansetron on discharge were recorded. An evaluation of response rates in hospital patients based on exposure to antineoplastic regimens causing acute (within 24 h) or delayed emesis (after 24 h) was formulated after data collection. Off-label use was summarized. RESULTS: Surveys from 197 of the 210 patients enrolled were complete for evaluation. Ondansetron was used to treat chemotherapy-induced emesis in 88 percent of the patients and 12 percent received it for various other indications. Ondansetron dosing was off-label in 15 percent and 73 percent prior to and after an emetogenic exposure, respectively. Twenty-six percent of the patients were younger than four years. Dosages ranged from 0.15 to 0.45 mg/kg, given in various schedules. The injectable form was given both intravenously and orally. There was a significant difference in the mean number of doses in hospital (9 ± 7.3) versus clinic (2 ± 1.5) patients (p<0.0001). Eighty-seven percent of all patients had a complete or major overall response. Possible ondansetron-associated adverse reactions were similar to those of previous reports for all patients, although some recorded reactions are not currently included in package labeling. CONCLUSIONS: This study documents off-label use of ondansetron in children. Further study of ondansetron use in children less than four years of age, and for indications other than chemotherapy-induced emesis, is needed. Additional evaluation into the most cost-effective dosing of ondansetron would also be valuable.

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Managing Immune Thrombocytopenic Purpura in infants: is it time to think of Eltrombopag?

10.22541/au.161387665.57523888/v1 ◽

2021 ◽

Author(s):

Giulia Ceglie ◽

Giulia Nocentini ◽

Francesca de Gennaro ◽

Vitangelo Clemente ◽

Margherita Di Mauro ◽

...

Keyword(s):

Complete Remission ◽

Adverse Effects ◽

Immune Thrombocytopenic Purpura ◽

Discontinue Treatment ◽

Off Label Use ◽

Thrombocytopenic Purpura ◽

First Report ◽

Off Label ◽

Robust Evidence ◽

Label Use

We report 2 cases of infants with acute and persistent Immune Thrombocytopenic Purpura (ITP) treated with Eltrombopag. Since ITP is rare in infants, robust evidence about how to treat these patients is not available. Both children underwent multiple lines of treatment without success and were successfully managed with off-label use of Eltrombopag. We did not observe any of the reported adverse effects of the drug and complete remission was achieved in both cases. In one child, we were able to discontinue treatment without any ITP relapse. This is the first report of an off-label use of Eltrombopag in infants.

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