P094 DIASTASIS POST-PREGNANCY PROGRAM

Abstract Aim This study aims to summarize our knowledge in rectus abdominis diastasis based on the experience collected by the multidisciplinary program. Material and Methods Retrospective analysis of a prospective database. The diastasis post-pregnancy program is an interdisciplinary protocol that aims to restore the anatomical and functional structure of the abdominal wall after the degenerative process of pregnancy. Used a systematic multidisciplinary evaluation that included an abdominal walls surgeon, plastic surgeon, physiotherapist, and radiologist. Following the findings, we propose a classification, adapting the specific treatment according to the degree of the patient's condition. Grade I only performed physiotherapy; Grade II: started physiotherapy plan, with associated surgical treatment due to lack of response; Grade III underwent surgery as the first treatment in addition to physiotherapy protocol. Endoscopic-assisted linea alba reconstruction plus mesh have using to repair midline hernias in association with diastasis. Results From January 2017 and June 2019, 1085 patients completed the program. Clinical classification: Grade I: 760 patients (70 %) and Grade II: 248 patients (64%) performed physiotherapy as first-line treatment, with associated surgical treatment being necessary for 89 patients (36%); Grade III: 77 patients (7%) underwent surgery as first-line treatment, associated with physiotherapy postoperative protocol. Postoperative complications were: 31 seromas(14%) , 11 omphalitis (5%), 5 hematoma (2%) 1 (0.44%) required surgical dressing. Mc Gill and Us Check-up post-treatment test showed improvement in 77 % of patients. Please insert your text here. Conclusions Evaluation and treatment, in post-pregnant patients, using a multidisciplinary approach concept showed good initial results with important improvement anatomical, functional, clinical, and aesthetic.

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Aplastic Anemia in the Elderly: A Nationwide Survey on Behalf of the French Reference Center for Aplastic Anemia

Blood ◽

10.1182/blood-2018-99-113359 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1298-1298

Author(s):

Adrien Contejean ◽

Matthieu Resche-Rigon ◽

Jérôme Tamburini ◽

Marion Alcantara ◽

Fabrice Jardin ◽

...

Keyword(s):

Aplastic Anemia ◽

Charlson Comorbidity Index ◽

Research Funding ◽

Performance Status ◽

Line Treatment ◽

First Line ◽

Advisory Committees ◽

Comorbidity Index ◽

Grade Iii ◽

First Line Treatment

Abstract Introduction Aplastic anemia (AA) is a rare but potentially life-threatening disease that frequently occurs in older patients. Various therapeutic options can be proposed and data regarding the ideal first line treatment of AA in this ageing population remains scarce. Methods We conducted a retrospective nationwide multicenter study in France to examine current treatments for AA patients over 60 years old within a 10-year period (1/1/2007 to 12/31/2016). Our aims were to evaluate efficacy and tolerance of AA treatment, and to analyze predictive factors for response and survival. Patients who were diagnosed with AA by a bone marrow biopsy at the age of 60 or over were included in the study. Results Over the course of a decade, 88 patients (median age 68.5) were identified in 19 centers, with a median follow-up of 32.1 months; 49% were women, the median Charlson comorbidity index was 2 (range 0-6), the median performance status was 1 (range 0-3), 21% had very severe (vSAA) and 36% severe AA. We analyzed 184 treatment lines which comprised ATG-CsA (33%, including 72% with horse ATG), CsA alone (14%), androgen alone (14%), eltrombopag alone (10%), CsA associated with androgen or eltrombopag (9%), and other treatments (20%). First-line treatment was ATG-CsA for half of patients. Comparisons of patients treated in first line with ATG-CsA, CsA or other treatments revealed that patients receiving ATG-CsA were significantly younger (66 years, vs. 71.5 vs. 71.5, respectively, p=0.007), more frequently female (61%, vs. 50% vs. 27%, p=0.02) and had a lower platelet count (8x109/L, vs. 12x109/L vs. 15x109/L, p=0.025). We found no difference with respect to weight, Charlson comorbidity index score, performance status or disease severity between first line treatment regimens. After first-line therapy, 32% of patients achieved a complete response (CR), and 15% a partial response (PR). After the 181 assessable treatment lines, 19% achieved CR and 19% a PR. Median time until best response was 151 days. The overall response rate (ORR) was 62% with ATG-CsA (70% as a first-line treatment), 35% with CsA alone (39% as first-line), 22% with eltrombopag, and 21% with androgen. The ORR in patients over 70 years receiving ATG-CsA (n=16) was 81% (50% achieving a CR). Responses were significantly better in first line and in patients with good performance status, as well as in those that had received ATG-CsA (ORR of 70% after first-line treatment). In a multivariable analysis using ATG-CsA as a baseline, we found that CsA alone (OR 0.35 (0.13;0.96), p=0.042), eltrombopag (OR 0.12 (0.03;0.54), p=0.0057) and androgens (OR 0.17 (0.05;0.58), p=0.0047) were all individually associated with lower response rates. The main complications were infections (grade III/IV, 35% of treatment lines including 9 deaths (5%)), and renal issues (grade-III/IV, 29%). ATG-CsA was associated with significantly more infectious complications (72% vs. 24%, p<0.0001), cardiovascular complications (32% vs. 15%, p=0.01) and acute kidney failure (43% vs. 22%, p=0.003) than other treatments. Patients aged 70 and over receiving ATG-CsA did not experience more complications than younger patients. Four clonal evolutions were recorded: two abnormal karyotypes (1 monosomy of chromosome 7 and 1 t(3;4)), one case of acute myeloid leukemia, and one case of myelodysplastic syndrome with 17% excess blasts. Three-year survival was 74.7% (median survival 7.36 years, Figure) and 24 patients died (nine infections, five deaths in palliative care or after active treatment had finished, four hemorrhagic complications, and six miscellaneous causes). Age (OR 1.07 (1.01;1.14), p=0.03), Charlson comorbidity index (HR 1.34 (1.07;1.67), p=0.01) and vSAA (HR 3.67 (1.51;8.91), p=0.004) were independently associated with mortality. Conclusion Our study showed a significantly better ORR with ATG-CsA than other regimens for treatment of AA in elderly, with more complications but no more death. Age per se is not a limiting factor for treatment with ATG-CsA: this regimen should be used as first-line treatment in elderly patients if they have a good performance status and low comorbidity index score. Among patients with adverse performance status or comorbidities contra-indicating the use of ATG, CsA alone or in combination may be safely used. Other strategies might be reserved for later courses of treatments. Supportive care may have a great impact on survival in this population. Disclosures Ades: JAZZ: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; silent pharma: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Peffault De Latour:Pfizer Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

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Intra-Arterial Catheter Guided Steroid Administration For The Treatment Of Steroid-Refractory Intestinal GvHD

Blood ◽

10.1182/blood.v122.21.4604.4604 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4604-4604

Author(s):

Michael Medinger ◽

David Buergler ◽

Jakob Passweg ◽

Arne Fischmann ◽

Christoph Bucher

Keyword(s):

Median Time ◽

Adult Patients ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Steroid Administration ◽

The Mean ◽

Grade Iii ◽

First Line Treatment ◽

Steroid Refractory

Background Acute gastrointestinal GvHD (GI-aGvHD) refractory to first line treatment with systemic corticosteroids is resulting in death in the majority of patients. Intra-arterial local dose intensification in the gut has been reported in pediatric but not in adult patients. We prospectively assessed the feasibility and efficacy of regional intra-arterial steroid treatment in adult patients with severe (>= grade III) GI-aGvHD not responding to first line treatment. Patients and Methods Patients with more than +++ GI-aGvHD not responding to intravenous methylprednisolone at a dose of 2 mg/kg/day within 14 days were eligible for inclusion. Catheter guided intra-arterial steroid administration (IASA) was performed by accessing the right or left common femoral artery; a 4 Fr angiography catheter was used to locate and select the superior and inferior mesenteric artery and, in patients with upper gastrointestinal symptoms into the celiac trunk (9 patients) and the left gastric artery (2 patients). The mean total dose of methylprednisolone administered over 1 minute was 180 mg (120-240 mg). In 7 patients with persistent or recurring symptoms, IASA was repeated within 14 days. Response assessment was at 28 days after IASA. CR was defined as complete resolution of GI symptoms; partial response was defined as reduction of GI score from +++ to ++. Non-response was defined as the same grade of aGvHD, progression of symptoms or death within 28 days after IASA. Results Between January 2010 and June 2012, 12 consecutive patients with steroid-refractory GI-aGvHD received IASA as second line treatment. The patient's baseline characteristics are summarized in Table 1. The mean patient's age was 53 years (range 30 - 69), 9 were male and 3 female. All patients received peripheral blood stem cells as stem cell source. All 12 patients had grade III GI-aGvHD. At time of initial IASA, 4 patients had skin (grade + - +++) and 2 patients had liver (grade +) involvement. In all patients the overall grade of aGvHD was III. The median time from HSCT to onset of GI-aGvHD was 20 days (range 6 - 278). The median time from onset of GI-aGvHD to initial IASA was 19 days (range 9 - 41). 7 patients not responding to the first IASA received a second IASA (median period of time between IASA was 13 days, range 6 - 14). 83% of patients had gastrointestinal response including four patients (33%) with complete response at 28 days after IASA (Table 2). 6/12 patients were alive at a median time of 531 days (389 – 1362) after IASA. During IASA no technical complications occurred. There was one duodenal ulcer in one patient two days after second IASA that resolved after treatment. Conclusion Regional treatment of severe GVHD with IASA treatment seems to be a safe and effective second line treatment for steroid-refractory GI-aGvHD in adult patients. Our results compare favorably with reported results of steroid-refractory GI-aGvHD. Disclosures: No relevant conflicts of interest to declare.

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P14.96 Gliomatosis cerebri imaging pattern: a treatment-independent marker for worse overall survival in WHO grade II and III gliomas

Neuro-Oncology ◽

10.1093/neuonc/noz126.331 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii90-iii91

Author(s):

I Divé ◽

E Steidl ◽

M Wagner ◽

M C Burger ◽

K Franz ◽

...

Keyword(s):

Growth Pattern ◽

Gliomatosis Cerebri ◽

Rank Test ◽

Line Treatment ◽

Control Cohort ◽

First Line ◽

Who Grade ◽

Log Rank Test ◽

Grade Ii ◽

First Line Treatment

Abstract BACKGROUND The term gliomatosis cerebri (GC) refers to glial brain tumors with widespread tumor expansion affecting three or more cerebral lobes. Formerly considered a distinct tumor entity, recent studies found no difference in the mutational profile of glial tumors with GC growth pattern compared to non-GC gliomas. Thus, in the new WHO classification of brain tumors, GC is no longer included as a separate diagnosis. While the presence of gliomas with GC growth pattern is associated with worse overall survival (OS), the underlying factors remain to be identified. Here, we asked whether differing therapeutic strategies in first line treatment could account for the worse outcome of patients with GC growth pattern and grade II and III histology. MATERIAL AND METHODS From the patient data bank of the University Cancer Center (UCT) Frankfurt, 47 patients with histological diagnosis of WHO grade II or III glioma, and with record of GC imaging pattern were identified. GC tumor expansion was confirmed by review of MRI scans prior to treatment initiation. Patients with WHO grade II or III glioma without GC growth pattern served as control cohort (n=379). IDH mutational status was available for 75% of GC tumors (IDH R132H mutated 32%; non-mutated 43%) and 69% of non-GC tumors (IDH R132H mutated 57%; non-mutated 12%). RESULTS Within the GC patient cohort, patients with tumors without contrast enhancement, lower WHO grade and mutated IDH status showed better OS. Compared to the control cohort, patients with GC had significantly shorter OS. This was independent of histological diagnosis or IDH mutation status. Patients with GC more frequently underwent radiochemotherapy (17% vs. 9% in the non-GC cohort), and drastically more often received chemotherapy alone (51% vs. 5%). We then analyzed OS in GC and non-GC patients that had received the same first line treatments. For radiochemotherapy in GC versus non-GC patients, OS was 1.1 years vs. 12.7 years (p =0.0075, log-rank test). For upfront chemotherapy alone, OS was significantly shorter in the GC cohort than in the non-GC cohort (3,6 years vs. undefined, p =0.0016, log-rank test). CONCLUSION Differences in first-line treatment cannot account for the worse prognosis of patients with GC imaging pattern. Further studies are needed to pinpoint biological or clinical factors that might influence responsiveness to therapy and prognosis of GC tumors.

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Chemotherapy for adult patients with spinal cord gliomas

Neuro-Oncology Practice ◽

10.1093/nop/npab017 ◽

2021 ◽

Author(s):

Dorothee Gramatzki ◽

Jörg Felsberg ◽

Bettina Hentschel ◽

Oliver Bähr ◽

Manfred Westphal ◽

...

Keyword(s):

Spinal Cord ◽

Specific Treatment ◽

World Health ◽

Line Treatment ◽

Imaging Data ◽

First Line ◽

Response To Chemotherapy ◽

Spinal Cord Glioma ◽

Best Responses ◽

First Line Treatment

Abstract Background The incidence of spinal cord gliomas, particularly in adults is low, and the role of chemotherapy has remained unclear. Methods We performed a multicenter, retrospective study of 21 patients diagnosed with spinal cord glioma who received chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by magnetic resonance imaging. Data on radiotherapy were taken into consideration. Results Thirteen patients were diagnosed with astrocytic gliomas World Health Organization (WHO) grades 1-4, the remaining eight patients with ependymomas WHO grades 1 or 3. Most patients had more than one neurosurgical intervention. Median age at time of first chemotherapy was 33 years (range 21-67 years). Seven patients had chemotherapy combined with radiotherapy as first-line treatment. Two patients had chemoradiotherapy at recurrence, without prior tumor-specific treatment beyond surgery. One patient received chemotherapy alone as first-line treatment and 2 patients had chemotherapy alone at recurrence, without prior treatment. Nine patients had received radiation therapy at an earlier time and chemotherapy was given at time of further recurrences. Best responses in astrocytomas were as follows: chemotherapy alone – 2 stable disease (SD), 3 progressive disease (PD); chemoradiotherapy – one complete response, 3 SD, 4 PD. Best responses in ependymomas were as follows: chemotherapy alone – one partial response, 5 SD, one PD; chemoradiotherapy – one SD. Conclusions Spinal cord gliomas represent a heterogeneous group of tumors. Survival outcomes in response to chemotherapy in adult spinal cord glioma patients vary substantially, but individual patients appear to derive benefit from chemotherapy.

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Imatinib Given Concurrently with Induction Chemotherapy Is Superior to Imatinib Subsequent to Induction and Consolidation in Newly Diagnosed Philadelphia-Positive Acute Lymphoblastic Leukemia (PH+ALL).

Blood ◽

10.1182/blood.v104.11.685.685 ◽

2004 ◽

Vol 104 (11) ◽

pp. 685-685 ◽

Cited By ~ 10

Author(s):

Oliver G. Ottmann ◽

Barbara Wassmann ◽

Heike Pfeifer ◽

Nicola Goekbuget ◽

Gesine Bug ◽

...

Keyword(s):

Hematologic Toxicity ◽

Induction Phase ◽

Line Treatment ◽

Rt Pcr ◽

First Line ◽

Imatinib Resistance ◽

Term Survival ◽

Log Reduction ◽

Grade Iii ◽

First Line Treatment

Abstract Background and study design: Despite intensive chemotherapy (ChThx), preferably followed by allogeneic SCT, the prognosis of adult patients with Ph+ALL is poor. Adding Imatinib to first-line treatment may improve efficacy and outcome and reduce the occurrence of Imatinib-resistance. However, it has not yet been established how Imatinib is best incorporated in front-line treatment of Ph+ALL. In a prospective, multicenter study of the GMALL, we compared the safety, anti-leukemic efficacy and MRD response of two strategies in which Imatinib was incorporated either intercurrently between (cohort 1) or simultaneously with (cohort 2) induction and consolidation cycles. Cohort 1 patients had to have a CR after induction therapy, with persistance of minimal residual disease (MRD) by RT-PCR; in contrast, patients in cohort 2 received Imatinib simultaneously with the 2nd phase of induction irrespective of remission status, with continuation of Imatinib for up to 8 weeks after the first consolidation cycle. Results: Cohort 1 encompasses 48 pts. (median age 47 y, range: 24–72), 46 of whom were in CR and 2 in PR upon starting Imatinib at 400 mg/d (n=36) or 600 mg (n=12). Imatinib was initiated 18 (5–52) days after completion of induction and given for a median of 28 (13–176) days. No patient relapsed during post-induction Imatinib, three pts. relapsed prior to SCT and one death occurred in CR after consolidation therapy due to septicaemia. Hematologic and non-hematologic toxicities were limited to WHO grades I/II. Cohort 2 encompasses 46 pts. (median age 39 y, range: 19–62) enrolled to date; 58% (19/33) had achieved a CR prior to initiation of Imatinib after induction phase I, a PR or non-response was documented in 18% and 24%, respectively. After completion of induction phase II concurrent with Imatinib, 96% (23/24 evaluable) had achieved a CR, one pt. (4%) failed and died. Comparison of median bcr/abl transcripts prior to and after induction II showed no significant decrease in cohort I (ChThx alone) in contrast to a 1.4 log reduction in cohort 2 (ChThx+Imatinib). Comparison of bcr/abl transcripts prior to consolidation I with pre-induction II levels showed a 3.9 log reduction in cohort 2 versus a 1.5 log reduction in cohort 1. Moreover, the frequency with which bcr/abl transcripts became undetectable by RT-PCR prior to consolidation I increased from 10% in cohort 1 to 50% in cohort 2. The duration of grade III/IV thrombocytopenia and neutropenia in cohort 2 was 12 (3–57) days and 16 (3–47) days, respectively, with cytopenias and/or infectious complications entailing Imatinib dose reductions in 40% and interruption of Imatinib in 77% of pts. The most frequent grade III/IV non-hematologic toxicity was hepatic (43% of evaluable pts.). There were no treatment related deaths. Summary: Imatinib given concurrently with and subsequent to induction and consolidation is highly effective first-line treatment for adult Ph+ALL, with a CR rate exceeding 90% and 50% MRD negativity. This strategy is more effective than alternating chemotherapy and Imatinib cycles, but is accompanied by substantial hematologic and non-hematologic toxicity. The overall impact on long-term survival in this very high risk group or patients remains to be determined, particularly in light of subsequent allogeneic SCT in a large proportion of patients.

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Autoinflation: Historical Highlights and Clinical Implications

Ear Nose & Throat Journal ◽

10.1177/014556139807700910 ◽

1998 ◽

Vol 77 (9) ◽

pp. 737-742 ◽

Cited By ~ 6

Author(s):

Sven-Eric Stangerup

Keyword(s):

Surgical Treatment ◽

Otitis Media ◽

Transient Condition ◽

Control Group ◽

Clinical Implications ◽

Line Treatment ◽

First Line ◽

Secretory Otitis Media ◽

Ventilation Tubes ◽

First Line Treatment

In 1563, Eustachius first described the tube that came to be named for him. In 1704, Valsalva described the maneuver that bears his name, and in 1836 Deleau became one of the first to advocate infusion of pure air through the eustachian tube using a catheter. Politzer devised his own method for actively inflating the middle ear without using a catheter in 1863. Most modern studies examining the use of autoinflation in the treatment of secretory otitis media have shown a beneficial effect, with effusion being cleared in 52 to 62% of ears up to nine months after the treatment. In two studies, no effect of autoinflation could be demonstrated, and in one publication the autoinflation group had deteriorated compared to the control group. In light of the fact that secretory otitis media is a benign and transient condition, that treatment with antibiotics or insertion of ventilation tubes is not without problems, and that the chance of improving the condition by autoinflation is approximately 50%, it is concluded that autoinflation should be considered first-line treatment, before antibiotic or surgical treatment is planned.

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Steroid-Refractory Acute Gvhd in Children: Retrospective Analysis of the AIEOP HSCT Registry

Blood ◽

10.1182/blood-2018-99-114862 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4578-4578

Author(s):

Marco Zecca ◽

Daria Pagliara ◽

Franca Fagioli ◽

Attilio Rovelli ◽

Edoardo Lanino ◽

...

Keyword(s):

Board Of Directors ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Advisory Committees ◽

Grade Ii ◽

Grade Iii ◽

Steroid Refractory

Abstract Introduction. Severe acute graft-versus-host disease (GVHD) remains the most relevant complication after allogeneic HSCT. Although its incidence in the pediatric population is lower than in adults, children with severe acute GVHD and who do not respond to first-line treatment with systemic steroids still have a poor prognosis. The exact incidence of steroid-refractory acute GVHD in children is still not precisely defined, as well as the risk of non-relapse mortality (NRM) due to steroid-refractory acute GVHD. Aim of our study was to analyze the frequency of acute GVHD unresponsive to first-line steroid treatment in children and adolescents given allogenic HSCT, to describe the second line treatment employed, and the outcome of patient with this complication. Patients and methods. This retrospective study included patients younger than 18 years at the time of transplantation and given a first allogeneic HSCT between 2010 and 2015 in one of the HSCT Centers of the Italian Association for Pediatric Hematology / Oncology (AIEOP). Overall, 1608 patients (59% M and 41% F) were analyzed. Median age at HSCT was 8 years (range 0.2 - 18) 1084 (67%) were affected by malignant diseases and 524 (33%) by non-malignant disorders. The donor was an HLA-matched family donor (MFD) in 28% of cases, an unrelated donor (UD) in 52% and an HLA-haploidentical family donor in 20%. In MFD transplants Cyclosporine (CSA) was used as GVHD prophylaxis in 30% of cases and the combination of CSA + short-term methotrexate (MTX) in 48%. 75% of UD transplant recipients received CSA + MTX + anti-thymocyte globulin (ATG) as GVHD prophylaxis, and 25% other drug combinations. Ex vivo T-cell depletion of the graft was employed in most patients given a HLA-haploidentical HSCT (79% of transplants), and high-dose post-transplant cyclophosphamide in 11% of cases. Results. The cumulative incidence (CI) of grade II-IV acute GVHD was 31%, while that of grade III-IV acute GVHD was 10%. The overall incidence of chronic GVHD was 13% and that of extensive chronic GVHD was 6%. The CI of NRM was 14% for grade 0 acute GVHD patients, 9% for grade I, 11% for grade II, 26% for grade III and 68% for grade IV (P < 0.001). Of the 491 patients with grade II-IV acute GVHD, 250 (51%) required a second-line treatment after first-line steroid therapy (30% of grade II, of 75% grade III and 83% of grade IV patients). Acute GVHD requiring second-line treatment was more frequent in UD transplant recipients (21% of patients) than in matched sibling or haploidentical donor recipients (7% and 13% respectively, P < 0.01), while age at HSCT and diagnosis (malignant vs. non-malignant disease) were not associated with this complication. Second-line treatment was extracorporeal photochemotherapy in 60% of patients, mofetil mycophenolate (MMF) in 46%, mesenchymal stromal cells (MSC) in 12%, monoclonal antibodies (MoAbs) in 5% and other treatments in 28%; 32% of patients received more than one second line treatment. Overall NRM was 13% for patients with grade 0-I acute GVHD, 15% for grade II-IV responding to steroids, and 25% for grade II-IV patients requiring second-line therapy (P < 0.001). The addition of a second-line treatment partially decreased NRM only in patients with grade IV acute GVHD, but the difference was not statistically significant (66% vs. 78%; P = 0.313). In multivariable analysis, grade III (HR = 1.84; P = 0.044) and grade IV acute GVHD (HR = 7.07; P < 0.001), and the use of an UD (HR = 1.63; P = 0.007) were associated with an increased NRM, while the use of a second-line treatment did not decrease this risk (HR = 0.80; P = 0.368). Conclusions. Despite being less frequent than in adults, severe steroid-refractory acute GVHD is still associated with a very high NRM also in pediatric patients. Second or third-line treatments adopted so far have not been effective in improving control of the complication and in decreasing NRM. The prospective evaluation of acute GVHD biomarkers (such as ST2 and REG3α) could help in identifying patients at higher risk of NRM. Prospective studies are warranted to define new treatment modalities that could decrease the mortality rate associated with the most severe form of disease. Disclosures Zecca: Chimerix: Honoraria. Locatelli:bluebird bio: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria.

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Alemtuzumab as First Line Treatment in Children with Familial Lymphohistiocytosis

Blood ◽

10.1182/blood-2019-124477 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 80-80 ◽

Cited By ~ 1

Author(s):

Despina Moshous ◽

Coralie Briand ◽

Martin Castelle ◽

Laurent Dupic ◽

Guillaume Morelle ◽

...

Keyword(s):

Pilot Study ◽

Outcome Measures ◽

Prospective Trial ◽

Specific Treatment ◽

Secondary Outcome ◽

Sustained Remission ◽

Line Treatment ◽

First Line ◽

Hematopoietic Stem ◽

First Line Treatment

Background Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition caused by uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines. When untreated, primary HLH is invariably fatal. Treatment requires the achievement of remission of HLH prior to allogeneic hematopoietic stem cell transplantation. Despite significant treatment progress, pre-HSCT mortality remains a challenge. In the Etoposide-based HLH-94 and HLH-2004 studies pre-HSCT mortality was 27% and 19%, respectively. A better understanding of the pathophysiology of primary HLH has opened new avenues for targeted immunotherapy. Based on our previous observation concerning the use of Antithymoglobulin in HLH, we propose a new therapeutic strategy with Alemtuzumab in association with steroids and cyclosporine A (CSA) as first line treatment in primary HLH. In contrast to ATG, Alemtuzumab does not activate T lymphocytes while killing them. Therefore, we expect a better tolerance and efficacy of Alemtuzumab. This may have a positive impact not only on survival until HSCT, but also on overall survival and quality of life, especially with regard to long-term neurological sequelae. Methods 24 consecutive treatment naïve patients with genetically confirmed primary HLH had received first line Alemtuzumab in association to steroids and CSA from 01/2009 to 06/2015 in the Unit for Pediatric Immunology in Necker Hospital Paris, as well as two additional patients in 10/2016 and 10/2018 respectively, who could not be included in the prospective trial. From 06/2015 to 06/2019, 29 patients have been enrolled in a multicenter, open, phase I/II, non-comparative, non randomized study (NCT02472054). Patients with lymphohistiocytic activation syndrome who had not received any specific treatment prior to enrollment except steroids and CSA were included. Treatment consisted in intravenous administration of Alemtuzumab in association to Methylprednisolone and CSA. The primary outcome measures is the number of surviving patients until HSCT, secondary outcome measures the number of complete remissions following treatment at Day (D)14, D21, D28. To assess the efficacy of the Alemtuzumab, the time of delay between the first administration of Alemtuzumab and complete remission will be determined. Alemtuzumab Pharmacokinetics will be done. All adverse events are reported. Results Retrospective analysis of 26 patients (pilot study): The median age of patients was 1.9 months (birth - 7 years), 6 patients were neonates. When Alemtuzumab was started, out of 26 patients 12 (46.1%) required intensive care, 8 (30.7%) mechanical ventilation, 13 (50%) had neurological involvement, 9 (34.6%) hepatocellular insufficiency. One 2-month-old Munc13-4 patient died at H+48 after two administrations of Alemtuzumab (total dose 1.5mg/kg) for hepatic failure and acute renal failure. A second patient with Perforin deficiency did not respond neither to three courses of Alemtuzumab (cumulative dose 6.5mg/kg) nor repeated Etoposid, 40mg/kg ATG, or Ruxulotinib. He died at D+65. The 24 remaining patients survived until HSCT (survival 92.3%). As shown in the figure, two patients required additional treatment. Overall 22 patients achieved CR, 2 PR at the time of HSCT. The prospective study enrolled 29 patients from 06/2015 to 06/2019. Median age at onset of HLH was 0.5 years (range 0.02 to 17.2 years), one patient withdrawed consent. 12 patients received one course, 13 two, 2 three and one patient 4 courses of Alemtuzumab. 24 patients with a genetic confirmed HLH predisposition reached the primary endpoint with 22 surviving until HSCT (91,6%). One patient is still awaiting HSCT. The three remaining patients are one CA-EBV patient and a newborn with secondary HLH due to fulminant HSV hepatitis, who both died, as well as a patient with predominant neurological HLH without genetic diagnosis who is in sustained remission without any specific treatment. Detailed results from the completed study will be presented. Conclusions This is the first report on Alemtuzumab as first line approach in the treatment of primary HLH. Our results in more than 50 pediatric patients treated in a pilot study and prospective trial indicate that Alemtuzumab allows controlling HLH activity with a favorable safety and tolerability profile in a very fragile population. 92.3% and 91.6% of patients respectively survived to HSCT. Figure Disclosures No relevant conflicts of interest to declare. Off Label Disclosure: Alemtuzumab (Campath) has been used in a prospective trial to evaluate its efficacy as first line treatment in Familial Lymphohistiocytosis.

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Capecitabine combined with Irinotecan (CapIri) as first line treatment of advanced colorectal carcinoma (ACRC): A phase ll study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13569 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13569-13569

Author(s):

J. Zidan ◽

W. Basher ◽

J. Shnaider ◽

S. Tmam ◽

A. Abzah ◽

...

Keyword(s):

Response Rate ◽

Progression Free Survival ◽

Outpatient Basis ◽

Line Treatment ◽

First Line ◽

Female Ratio ◽

Free Survival ◽

Medical Disorders ◽

Grade Iii ◽

First Line Treatment

13569 Background: The combination of 5-FU + LV with irinotecan as first line treatment of advanced colorectal cancer (ACRC) has shown higher response rate compared with 5-FU +LV with the same progression free survival. Capecitabine is more active than 5-FU.The aim of this study is to determine the side-effect profile, dose limiting toxicity and response rate to CapIri combination as first line treatment in ACRC, on an outpatient basis. Methods: Inclusion criteria: age >18–75 years, ECOG ≤ (0–3), measurable disease, no previous treatment for advanced disease, previous adjuvant chemo-therapy more than 6 months is allowed, signed informed consent and adequate hepatic, renal and hematological function. Exclusion criteria: Serious concurrent medical disorders, prior other malignancy, pregnancy or breast-feeding and patients with poor compliance. Capecitabine 1000mg/m2 twice daily was given for 14 days followed by 7 days rest and Irinotecan (100mg/m2) was given days 1 and 8. Treatment was repeated on day 2. Results: 28 patients (pts) were included. All patients were assessable for response and toxicity. Average age was 64 years, male/female ratio 20/8. Fourteen pts had liver metastases, 5 had lung and 9 had abdominal metastases. Median No of cycles was 4. Grade III and IV diarrhea was observed in 12 (44%) pts, vomiting in 9 (31%) pts, fatigue in 12 (44%) pts, grade IV leucopenia in 5 (17%) pts. Complete response was achieved in 3 (11%) pts, partial response in 15 (53%), stabilization of disease in 5 (18%) and tumor progression in 5 (18%) pts. Progression free survival is 8.4 months. Overall survival is not yet available. Conclusions: This regimen appears feasible with acceptable toxicity except for grade III diarrhea, on an outpatient treatment basis, with significant antitumor activity, without the requirement for indwelling catheters. It is also feasible for older patients. No significant financial relationships to disclose.

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R-CHOP Vs. R-CHOP+X for Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2019-126013 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5331-5331

Author(s):

Oren Pasvolsky ◽

Alon Rozental ◽

Pia Raanani ◽

Anat Gafter-Gvili ◽

Ronit Gurion

Keyword(s):

Adverse Events ◽

Disease Control ◽

Cell Lymphoma ◽

Meta Analysis ◽

B Cell Lymphoma ◽

Line Treatment ◽

First Line ◽

Large B Cell Lymphoma ◽

Grade Iii ◽

First Line Treatment

Introduction: Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has remained the standard of care as first line treatment for diffuse large B-cell lymphoma (DLBCL) for almost two decades. Treatment outcomes are still suboptimal, as approximately 40% of patients have refractory disease or relapse. Prospective studies recently examined whether the addition of various drugs to R-CHOP (termed R-CHOP+ X) could improve outcomes. The aim of this study was to compare the efficacy and safety of R-CHOP vs. R-CHOP +X as first line treatment for DLBCL. Methods: Systematic review and meta-analysis of randomized controlled trials including patients with DLBCL, comparing first line treatment with R-CHOP vs. R-CHOP+X (i.e. R-CHOP with the addition of another single drug). The Cochrane Library, MEDLINE, conference proceedings and references were searched until June 2019. Two reviewers appraised the quality of trials and extracted data. Primary outcome was overall survival (OS). Secondary outcomes included overall response rate (ORR), complete response (CR) rate, disease control and safety. Results: Our search yielded seven trials conducted between the years 2010 and 2019, including 2939 patients (three abstracts, and four published in peer review journals). Median age of patients ranged between 50 to 67 years. The added drug was bortezomib and lenalidomide - each drug in two trials; gemcitabine, bevacizumab and ibrutinib - each drug in one trial. Three trials included all DLBCL patients regardless of cell of origin, whereas four trials included only patients with non-GCB DLBCL. Characteristics of trials included in the meta-analysis are described in Table 1. Regarding OS, the point of estimate favored improved OS with R-CHOP+X as compared to R-CHOP, yet without statistical significance, HR 0.87, [95% confidence interval (CI) 0.73-1.04, I2=0, 1984 patients, 5 trials]. The ORR and CR rates were similar in the two arms (RR 0.97 [95% CI 0.93-1.02, I2=65%, 2824 patients, 7 trials], and RR 0.99 [95% CI 0.93-1.05, I2=37%, 2826 patients, 7 trials], respectively). However, there was a trend towards improved disease control in the RCHOP+X arm, HR 0.89 [95% CI 0.78-1.01, I2=36]. Regarding safety, three trials (N=1200) reported serious adverse events. There was a significant increase in adverse events in the R-CHOP+X group, RR 1.42 [95% CI 1.24-1.64. I2=55%]. In addition, there was more hematologic toxicity in the R-CHOP+X arm, as reflected by higher rates of grade III/IV thrombocytopenia, anemia and neutropenia. Conclusions: The addition of an extra drug to the conventional first line R-CHOP regimen in patients with DLBCL resulted in a trend towards improved disease control compared to standard R-CHOP. However, there was no significant change in response rates or OS, and R-CHOP+ X was associated with an increased risk for serious and grade III/IV hematological adverse events. R-CHOP still remains the "gold standard" of treatment for DLBCL. Further analyses could perhaps reveal subgroups that would benefit from the addition of an additional drug to this regimen. Disclosures Gurion: Roche: Consultancy.

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