Low-Level FLT3-ITD Mutations Do Not Predict for Higher Relapse Rate in AML with Standard Risk Karyotpye.

Abstract Abstract 1591 Poster Board I-617 High-level FLT3-ITD mutations predict for a higher relapse rate and inferior survival among patients with standard risk karyotype AML. The influence of low-level FLT3-ITD mutations is less clear, although the MRC group (Gale et al, 2008) reported that low-level mutations are associated with an inferior prognosis as compared to an unmutated group. In the absence of FLT3-ITD, NPM1 mutations predict for a lower relapse rate. We analyzed outcomes of intensive chemotherapy in patients with standard risk karyotype AML (n=131) between 2004-2008. Patients received uniform induction chemotherapy consisting of cytarabine plus daunorubicin (7+3), followed by 2 consolidations consisting of high-dose cytarabine plus daunorubicin for pts under age 60 (n=96) or 7+3 followed by NOVE for pts age 60+ (n=35). Patients were divided into 3 groups based on the ratio of FLT3-ITD:FLT3-wt: There were 73 patients with negative FLT3-ITD (defined as FLT3-ITD:wt ratio < 0.01), 30 patients with low-level ITD (ratio > 0.01 – 0.37), and 28 patients with high-level ITD (ratio > 0.37). The mean presenting WBC was 32.2 ×109/L in the group with negative ITD, 49.4 ×109/L in the group with low-level ITD and 97.2 ×109/L in the group with high-level ITD (p < 0.0001). At a median follow-up of 19 months (range 2-95 months), the median OS of the entire group was 21.3 months. Patients with high-level ITD had a significantly inferior RFS (p = 0.0009) and OS (p = 0.003) as compared to the low-level and negative groups. Comparing the negative ITD and low-level ITD groups, there was no significant difference in RFS (p = 0.65) or OS (p = 0.18). The frequency of NPM1 mutations was not significantly different between these two groups (42% vs. 35%). These data were re-analyzed using a different cutoff according to % FLT-ITD positivity: negative < 1% (n=73), low-level 1 – 50% (n=42), high level > 50% (n=16). Using these ranges, the low-level FLT3-ITD group had a significantly lower CR rate (74% vs. 93%, p = 0.004) and OS (36% vs. 61%, p = 0.01) as compared to the group with negative FLT3-ITD, but there was no significant difference between these two groups with respect to RFS (2 year RFS 48% in low-level ITD group vs. 40% in negative ITD group). The high-level ITD group demonstrated significantly inferior RFS (p = 0.02) and OS (p = 0.01) as compared to the other two groups. These findings confirm the poor prognosis associated with high-level FLT3-ITD mutations due to high relapse rates. However, in contrast to previously reported data, we did not find that low level FLT3 –ITD mutations were associated with inferior RFS, although we did find, unexpectedly, that this low-level group had a lower CR rate. Disclosures No relevant conflicts of interest to declare.

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Gemcitabine, Dexamethasone and Cisplatin (GDP regimen) As First Salvage Treatment of Patients with Refractory or Relapsed Diffuse large B Cell Non Hodgkin Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v118.21.2696.2696 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2696-2696

Author(s):

Thoraya Mohamed Abdel Hamid ◽

Mona fawzy Ramadan ◽

Abeer Bahnassy ◽

Fouad Abu- Taleb ◽

Magdy Saber

Keyword(s):

Conflicts Of Interest ◽

High Dose ◽

Chemotherapy Response ◽

Non Hodgkin Lymphoma ◽

Study Results ◽

Significant Difference ◽

Duration Of Response ◽

Relapsed Disease ◽

Time To Relapse

Abstract Abstract 2696 Background: Many chemotherapy regimens have been used for patients with refractory or relapsed DLBCL. No regimen has demonstrated superiority to another in this setting. Specific markers could predict the response to certain agents. Aim: to evaluate the response of GDP regimen in relapsed and refractory DLBCL patients and to assess ribonucleotide reductase subunit M1 (RRM1) as a possible predictor marker to Gemcitabine response. Patients and method: Patients with Relapsed or refractory DLBCL after one previous anthracycline-containing chemotherapy regimen were treated with the GDP regimen. RRM1 was assessed by immunohistochemistry in 55 cases and its expression was correlated to treatment outcome. Patients who could not proceed to stem cell transplantation (SCT) were followed for chemotherapy response and their results are presented. Results: The study included 70 patients with a median age of 40 years (range 18–73). At start of GDP, 19 patients (27.1%) were refractory and 51 (72.9%) were relapsed. After 4 cycles of treatment, 42 patients achieved CR, with a CR rate of 60% (95% CI: 53–68%). The median DFS was 6 months (95% CI: 5 to7 months), this DFS didn't include patients who underwent auto SCT. After a median follow-up of 20 months (range 6 to 30 months), the median OS of the patients who achieved CR was not reached, while those who didn't achieve CR had a median OS of 27.4 months (p= 0.01). Correlation between response and the pretreatment prognostic factors including IPI score or any of its elements, previous line of chemotherapy, time to relapse and status at time of salvage were studied with only significant difference in response to GDP between patients with refractory and those with relapsed disease (CR= 21.1% versus 60% respectively, p < 0.001). There was significant correlation between RRMI study results and response to GDP, 30/31 cases with low RRM1 expression achieved CR (96.8%), while only 7/24 cases with high expression achieved CR (29.2%), (p=0.001). No significant relation could be found between RRM1 expression and DFS. Conclusion: GDP regimen is active for patients with refractory or relapsed DLBCL however, the duration of response is short and high-dose therapy with SCT support is the reference postremission treatment. RRM1expression can predict response to Gemcitabine-based chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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Single Versus Tandem High Dose Therapy (HDT) Supported with Autologous Blood Stem Cell (ABSC) Transplantation Using Unselected or CD34-Enriched ABSC: Long-Term Results of a Two by Two Designed Randomized Trial in 225 Young Patients with Multiple Myeloma (MM). for the Group “Myelome-Autogreffe”, Caen, Creteil, Limoges, Paris, Strasbourg, France.

Blood ◽

10.1182/blood.v114.22.2320.2320 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2320-2320 ◽

Cited By ~ 2

Author(s):

Jean-Paul Fermand ◽

Kristell Desseaux ◽

Jean Pierre Marolleau

Keyword(s):

Randomized Trial ◽

Disease Progression ◽

Conflicts Of Interest ◽

Autologous Blood ◽

Prospective Trial ◽

Early Death ◽

Long Term Results ◽

High Dose ◽

Significant Difference

Abstract Abstract 2320 Poster Board II-297 In 1996, we initiated a multicenter prospective trial where patients aged under 56 with newly diagnosed symptomatic MM were randomly assigned up-front to receive either a single HDT (HDT1) or two sequential HDT (HDT2). In addition, all patients were independently randomized to be transplanted with unselected ABSC (unselected arm) or CD34-enriched ABSC (CD34 arm). We presented here updated data of this factorial 2*2 design trial, based on a median follow-up of 123 months.In all cases, patients first received one or 2 courses of high dose steroid containing regimens and ABSC were thereafter mobilized by cytoxan (CTX) (4 g/m2) and lenograstim (10 mg/kg/d). When appropriate (CD34 arm), part of collected ABSC were selected using the Isolex®300i system. The selection procedure resulted in a median purity of 95% (65-100) and in a more than two log tumor cell depletion. In the HDT1 arm, HDT was preceded by 3 monthly courses of a VAD-like regimen and combined a multi-drug regimen (carmustine, etoposide, melphalan 140 mg/m2 (MLP 140) and CTX 60 mg/kg) with a TBI (12 grays in 6 fractions). Patients treated in the HDT2 arm received MLP 140 alone (always supported by unselected ABSC) followed 2 to 3 months later by a second MLP 140 combined with etoposide (30 mg/kg) and 12-gray TBI. In both arms, TBI including HDT were supported with unselected or CD34 enriched ABSC. Two hundred and twenty-five patients were included in the study. Baseline characteristics of the four groups were close. All analyses were performed in intent to treat basis. In HDT groups, treatment completion rates were satisfactory, with 6/112 transplants not performed in the HDT1 group (allotransplant n=1, refusal n=1, mobilisation failure n=1, early death due to disease progression n=3) and 9/113 second transplant not performed in the HDT2 group (allotransplant n=2, mobilisation failure n=3, relapse post first transplant n=1, early death due to disease progression n=3). In the HDT1 and HDT2 groups, median time to TBI-including transplant was 4 months and 4.5 months, respectively.Present analysis did not show any significant difference in terms of early mortality, disease response and outcome of patients included in the two HDT groups. Early death rates (within 9 months post randomization, including toxic deaths and fatal progressive diseases) were 12% and 7% in the HDT1 and the HDT2 arms, respectively. At one year post-randomization, 32 (35 %) patients in the HDT1 and 32 (37 %) patients in the HDT2 groups were still in unmaintained CR or VGPR. The 2 OS curves were not statistically different (p= 0.60 by the log rank test), neither the EFS curves (p= 0.61). There was no significant interaction between selection CD34 and HDT in terms of outcomes. There was no evidence for benefit of CD34 selection as compared to the use of unselected ABSC. Of note, in the CD34 selected group, incidence of severe infections was increased. In conclusion, with a 10-years median follow-up, results of this randomized trial did not show any significant benefit of single HDT versus tandem HDT. Disclosures: No relevant conflicts of interest to declare.

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A Retrospective Real-Life Analysis of Chronic Myeloid Leukemia Patients in Suboptimal Response to Imatinib

Blood ◽

10.1182/blood.v120.21.4446.4446 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4446-4446

Author(s):

Dario Ferrero ◽

Elena Crisà ◽

Marco Cerrano ◽

Mario Boccadoro ◽

Francesca Pirillo ◽

...

Keyword(s):

Conflicts Of Interest ◽

Standard Dose ◽

Real Life ◽

Significant Risk ◽

Chronic Phase ◽

Cytogenetic Response ◽

High Dose ◽

Significant Difference ◽

Response Detection

Abstract Abstract 4446 Life expectancy of CML patients has greatly improved in tyrosine-kynase inhibitor (TKI) era, but still some questions remain about the management of suboptimal responders (SR) to imatinib standard dose. This group of patients appears to be heterogeneous, with significant differences in terms of event-free survival between cytogenetic SR and molecular SR (Alvarado et al, Cancer 2009) European Leukemia Net (ELN) recommendations did not clarify those differences and there isn't a clear agreement on SR: maintaining imatinib at standard or higher dose or switching to another TKI are all considered acceptable options (Baccarani et al, JCO 2009). We retrospectively analyzed 63 CML patients, diagnosed in chronic phase between 1988 and 2011, SR to imatinib 400 mg/d, treated according to the 3 different ELN options. Fifty-two patients received imatinib front line and 11 had been previously treated with an interferon based therapy. Sokal score, evaluable in 44 patients, was high in 7, intermediate in 24 and low in 12, respectively. Twenty-five patients were cytogenetic SR and 38 molecular SR. The median follow-up from diagnosis was 76 months (range 10–292). At suboptimal response detection 47 patients (74%) continued imatinib 400 mg/d (30 of them afterword switched to high dose imatinib or new TKI), 12 patients (19%) increased imatinib dose to 600 mg/d (7) or 800 mg/d (5) (8 of them later changed TKI) and only 4 patients switched immediately to new TKI. Twenty-three percent of the 47 patients who continued imatinib 400 mg/d obtained a stable complete cytogenetic response (CCyR) and major molecolar response (MMR) while 27% underwent to a failure. Globally thirty-tree SR patients increased imatinib dose, 36% at suboptimal response detection and 64% after a median of further 12 months of standard dose treatment (range 3–50): 48% of them obtained a durable CCyR and MMR. Twenty-six evaluable patients switched to new TKI (9 to nilotinib and 17 to dasatinib), 13 after high dose imatinib: 62% of the patients achieved a stable CCgR and MMR. Both high dose imatinib and new TKI were significantly more effective in achieving CCyR and MMR than maintaining imatinib 400 mg/d (p<0,05). Considering separately the subgroup of cytogenetic SR patients, a stable CcyR has been reached by 35% of patients continuing imatinib standard dose, by 50% of the patients who increased imatinib dose and by the totality of the patients treated with new TKI (option significantly superior to the other two, p<0,05). Among molecular SR, 26% of the patients obtained a stable MMR with imatinib 400 mg/d, 52% with imatinib 600 or 800 mg/d and 63% switching to new TKI. The difference was statistically significant between new TKI and imatinib 400 standard dose only (p<0,05). Cytogenetic SR maintained at imatinib 400 mg/d had a higher risk of event (defined as loss of hematologic or cytogenetic response or death) compared to molecular SR (40% vs 5%, p<0,01), although at the last follow-up, after a change in therapeutical strategy, no difference in response rate was detected between cytogenetic and molecular SR (68% vs 71%) in stable CCyR and MMR. Two patients progressed to accelerated phase (clonal evolution) but then obtained an optimal response after switching to new TKI; 2 patients died of unrelated disease. Among the 61 living patients, 71% was in MMR, 26% in CCyR only and 3% didn't reach CCyR (for these patients the efficacy of the therapeutic change is not evaluable yet). In our casistics cytogenetic SR had a higher risk of negative events than molecular SR, as reported in literature, although they obtained similar responses after changing therapeutic strategy. No clear advantage in maintaining imatinib 400 mg/d after suboptimal response was observed, since it led to a few optimal responses and was associated with a significant risk of treatment failure. Imatinib dose increment might represent a more reasonable option, at least for molecular SR. Considering the global casistic no significant difference in response rates were found between new TKI and high dose imatinib even if dasatinib and nilotinib showed a trend towards a superior efficacy in patients mostly unresponsive to the last option, suggesting that an earlier switch to new TKI might further increase the proportion of optimal responders. For cytogenetic SR the switch to new TKI brought better results than those obtained with high dose imatinib: therefore it seems to be the best choice in this subgroup of patients. Disclosures: No relevant conflicts of interest to declare.

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Different Impact of Expression Levels of IGFBP2 and IGFBP7 on Survival and Relapse Rate in Acute Promyelocytic Leukemia

Blood ◽

10.1182/blood.v126.23.1382.1382 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1382-1382

Author(s):

Anna Hecht ◽

Daniel Nowak ◽

Florian Nolte ◽

Verena Nowak ◽

Julia Oblaender ◽

...

Keyword(s):

Acute Promyelocytic Leukemia ◽

Prognostic Marker ◽

Relapse Rate ◽

Conflicts Of Interest ◽

Promyelocytic Leukemia ◽

Control Group ◽

High Dose ◽

Healthy Controls ◽

Expression Levels ◽

Significant Difference

Abstract Introduction: Insulin-like growth factor binding proteins (IGFBP) are carriers of insulin-like growth factors (IGFs). They prolong their half-life and modulate their availability and activity. The IGF-signaling system has been shown to have an important role in various solid cancers and hematologic malignancies. High levels of IGFBP2 and IGFBP7 have been associated with chemoresistance, relapse and inferior survival in different leukemias. Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), which has been reported to have increased expression of IGFBP2. However, there is no data on its impact on prognosis. In addition, no data exist on IGFBP7 in APL. The aim of this study was to elucidate the influence on prognosis of both candidate genes in APL patients. Methods: Expression levels of IGFBP2 und IGFBP7 were retrospectively analysed in bone marrow (BM) samples at the time of initial diagnosis from 69 APL patients (42 female, 27 male) after informed consent. Median age of patients was 46 years (range 19 to 82 years). All patients were diagnosed and treated in the German AML Cooperative Group (AMLCG) studies. Treatment consisted of simultaneous ATRA and double induction chemotherapy including high dose ara-C, one cycle of consolidation chemotherapy and 3 years monthly maintenance chemotherapy. In patients older than 60 years, the second induction cycle was at the discretion of the treating physician. Three patients (4%) received an induction of ATRA and an anthracycline without ara-C. BM samples of 22 healthy volunteers served as a control group. Multiplex reverse transcriptase quantitative real-time PCR (qRT-PCR) was performed on a LightCycler® 480 (Roche, Mannheim, Germany) PCR system. Glucose-6-phosphat isomerase was used as a housekeeping gene. For quantification of relative expression values a modified delta-delta CT calculation model according to Pfaffl was used after determination of PCR efficiencies. cDNA from the cell line K562 served as a calibrator in each run. All reactions were performed in triplicates. IGFBP2 expression groups were defined as follows: Patients with IGFBP2 expression below or equal the 25th percentile (IGFBP2low) were compared to patients with higher IGFBP2 expression (IGFBP2high). Overall survival (OS), relapse free survival (RFS) and the cumulative incidence of relapse (CIR) were calculated using the Kaplan-Meier method and a log-rank test was used to compare differences between the groups (p < 0.05). Results: Expression levels of IGFBP2 did not differ between APL patients and healthy controls. However, there was a significantly higher relapse rate in APL patients with low IGFBP2 expression (CIR: 25% in the IGFBP2low group vs. 5% in the IGFBP2high group; p=0.04). Accordingly, RFS of patients in the IGFBP2low group was also inferior (41% vs. 81% in the IGFBP2high group; p=0.0002; Fig. 1). The OS of patients who had responded to induction therapy was also influenced by IGFBP2 expression (OS of responders: 61% for IGFBP2low vs. 83% for IGFBP2high; p=0.02). However, there was no significant difference in the analysis of OS of all patients including patients who suffered early death. In contrast to these findings, IGFBP7 was expressed significantly lower in APL patients compared to healthy controls (p<0.0001) but there was no association with outcome of APL patients. Conclusion: Of the two analysed IGFBP family members only IGFBP2 showed impact on the prognosis of APL patients. Remarkably, IGFBP2 was not overexpressed compared to healthy controls in our patient cohort. The reason might be that whole BM samples of healthy controls were used instead of subpopulations. Still, among the APL patients cohort its expression showed a strong influence on prognosis especially on relapse rate and RFS. To find low expression as a negative prognostic marker is surprising as for leukemias only high expression has been reported as a negative factor. However, IGFBP2 has been proposed to suppress tumor development through binding IGFs and preventing IGF-receptor driven tumorigenesis. This is supported by the fact that the IGFBP2 promotor is hypermethylated in various types of cancer. In summary, we identified low IGFBP2 expression as a novel prognostic marker for APL. Further investigations are warranted to clarify its possible role in leukemia. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Lower Dosages of Intravenous Immunoglobulin (IVIg) in Treating Immune Thrombocytopenia with Long-Term Follow-up of Three Years

Blood ◽

10.1182/blood.v126.23.3480.3480 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3480-3480

Author(s):

Zeping Zhou ◽

Zhuoqing Qiao ◽

Huiyuan Li ◽

Xian Zhang ◽

Feng Xue ◽

...

Keyword(s):

Intravenous Immunoglobulin ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Ivig Treatment ◽

High Dose ◽

Significant Difference ◽

Long Term Follow Up ◽

Group A ◽

Group B

Abstract This study compared the effects of different dosages of intravenous immunoglobulin (IVIg) against immune thrombocytopenia. A total of 167 patients, 91 adults and 76 children, with ITP, followed-up for 3 years in the case-control study, were each divided into three subgroups according to the dosages of IVIg administered: group A (0.2g/kg/day), group B (0.3g/kg/day), group C (0.4g/kg/day). The therapeutic response in 91 adult patients did not differ significantly among the three groups of IVIg dosages (P=0.459). The response rate of IVIg treatment in the three adult groups was 97.1% for group A, and 97.2% for group B, 100% for group C. The mean time for raising platelets to 30 ×109/L in group A was 2.5 days, group B 3.2 days, group C 2.9 days (P=0.324). The median IVIg consumption in group A was 0.83 g/kg, group B 1.22 g/kg, and group C 1.64 g/kg (P<0.01). Similar results were shown in the children groups. The follow-up results showed no significant difference of clinical outcome between groups A, B and C. In conclusion, low-dose IVIg treatment is shown to be as effective as high-dose regimen without increasing the risk of developing the patients into chronic ITP conditions, suggesting that ITP patients could be treated more cost-effectively by lower than conventional dosage of IVIg regimen. Disclosures No relevant conflicts of interest to declare.

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Exploring The Effect of Visual Information Degradation on Human Perception and Performance In A Human-Telerobot System

Proceedings of the Human Factors and Ergonomics Society Annual Meeting ◽

10.1177/1071181320641310 ◽

2020 ◽

Vol 64 (1) ◽

pp. 1302-1307

Author(s):

Richard Stone ◽

Minglu Wang ◽

Thomas Schnieders ◽

Esraa Abdelall

Keyword(s):

Visual Information ◽

Human Perception ◽

Low Level ◽

Hit Rate ◽

Word Level ◽

Level Of Automation ◽

Significant Difference ◽

Human Operators ◽

And Performance ◽

High Level

Human-robotic interaction system are increasingly becoming integrated into industrial, commercial and emergency service agencies. It is critical that human operators understand and trust automation when these systems support and even make important decisions. The following study focused on human-in-loop telerobotic system performing a reconnaissance operation. Twenty-four subjects were divided into groups based on level of automation (Low-Level Automation (LLA), and High-Level Automation (HLA)). Results indicated a significant difference between low and high word level of control in hit rate when permanent error occurred. In the LLA group, the type of error had a significant effect on the hit rate. In general, the high level of automation was better than the low level of automation, especially if it was more reliable, suggesting that subjects in the HLA group could rely on the automatic implementation to perform the task more effectively and more accurately.

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SEOM clinical guideline for management of adult medulloblastoma (2020)

Clinical & Translational Oncology ◽

10.1007/s12094-021-02581-1 ◽

2021 ◽

Author(s):

R. Luque ◽

M. Benavides ◽

S. del Barco ◽

L. Egaña ◽

J. García-Gómez ◽

...

Keyword(s):

Residual Tumor ◽

Large Cell ◽

High Dose Chemotherapy ◽

High Dose ◽

Molecular Alterations ◽

Adult Medulloblastoma ◽

Group 4 ◽

Risk Patients ◽

Standard Risk

AbstractRecent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

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Etoposide Plays an Important Role in Treatment of Lymphoma Associated Hemophagocytic Lymphohistiocytosis

Blood ◽

10.1182/blood-2019-132119 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5341-5341

Author(s):

Yue Song ◽

Yini Wang ◽

Jingshi Wang ◽

Zhao Wang

Keyword(s):

Mortality Rate ◽

Hemophagocytic Lymphohistiocytosis ◽

Initial Treatment ◽

Conflicts Of Interest ◽

Remission Rate ◽

Total Mortality ◽

High Dose Chemotherapy ◽

High Dose ◽

Inflammatory Status ◽

Significant Difference

Background: Hemophagocytic lymphohistiocytosis (HLH) is a severe or even fatal inflammatory status caused by a hereditary or acquired immunoregulatory abnormality. It is divided into two categories: primary and secondary. Secondary HLH (sHLH) is often associated with and caused by infections, malignant tumors, and autoimmune diseases. Lymphoma associated HLH (LAHS) is one of the most common sHLH, usually presents worse prognosis higher mortality. The treatment strategy for LAHS is still controversial. Etoposide is one of the key drug in HLH-94/04 regimen. We sought to identify the importance of including etoposide in the initial treatment of LAHS, especially comparing with the high dose chemotherapy. Methods: The patients diagnosed as LAHS in our center between Jan 1 2015 and Dec 31 2017 were observed. Survival times were calculated from the date of diagnosis of HLH. All patients were followed up until death or 31 Dec 2018, whichever occurred first. Patients undergoing stem cell transplantation were censored on the date of that procedure. Results: There were 68 patients in total. The median age of the patients was 48 years (15-76 years). They were divided into two groups according to weather the initial treatment containing etoposide. There were 53 patients with initial etoposide and 15 without it. The baseline level between two group shows no differences (p>0.05). The treatment regimens with initial etoposide include HLH-94/04 regimen, DEP (doxorubicin-etoposide-methylprednisolone), L-DEP (PEG-aspargase and DEP regimen), E-CHOP (etoposide and CHOP regimen) and RE-CHOP; those without the initial etoposide, but high-dose chemotherapy, include CHOP/COP, R-CHOP/COP, L-CHOP, CVAD, L-GDP regimen and et al. The response rates of the 68 patients was 66.1%, with the CR rate of 25% (17/68) and PR rate of 41.1% (28/68). A total of 32 cases with initial etoposide achieved remission, and the remission rate was 71.7% (CR 28.3% and PR 43.4%). 7 cases with chemotherapy without etoposide achieved remission, and the remission rate was 46.7%. A significant difference was noted between the two groups (p<0.01). A total of 41 deaths occurred with a total mortality rate of 60.3%. There were 28 deaths in patients with initial etoposide (mortality rate 52.8%) and 13 deaths in the other group (mortality rate 86.6%). A significant difference in mortality was noted between the two groups (p=0.020). Comparing the long-time survival between two groups, the survival of the initial etoposide group (101w±13, 95%CI [76, 127]) is significantly better than that of the no initial etoposide group(37w±12.7, 95% CI [12.0, 61.9]) (p=0.43) (Figure 1). Conclusion: As one of the secondary HLHs, LAHS suffers the worst outcome among all the types of HLH. This study found that initial treatment including etoposide, comparing with the chemotherapy without etoposide, can provide higher response rate, lower mortality rate and better survival. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Pre-Enucleation Chemotherapy in Advanced Intraocular Retinoblastoma. Central America Follow Up: AHOPCA II

Journal of Global Oncology ◽

10.1200/jgo.2016.004440 ◽

2016 ◽

Vol 2 (3_suppl) ◽

pp. 75s-75s

Author(s):

Sandra Luna-Fineman ◽

Soad L. Alabi ◽

Mauricio E. Castellanos ◽

Yessika Gamboa ◽

Ligia Fu ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Central America ◽

Conflicts Of Interest ◽

Risk Group ◽

High Risk Group ◽

Globe Rupture ◽

Neo Adjuvant Chemotherapy ◽

Standard Risk

Abstract 57a Purpose: A significant percentage of patients in Central America present with buphthalmos, carrying a high risk of globe rupture and orbital contamination. In 2007, AHOPCA introduced chemotherapy before enucleation in children with buphthalmos. Methods: Patients with advanced intraocular disease were considered standard-risk and underwent enucleation. Those with diffuse invasion of choroid, postlaminar optic nerve, or anterior chamber invasion received 4-6 cycles of adjuvant chemotherapy (vincristine, carboplatin, etoposide). Patients with buphthalmos or perceived to be at risk for abandonment were considered high-risk, given 2-3 cycles of chemotherapy before enucleation to compete 6 cycles regardless of pathology. All cases were discussed via online meetings. Results: From 2007 to 2014, 396 patients were enrolled; 240 had IRSS stage I (174 unilateral). 143 had upfront enucleation, 95 had pre-enucleation chemotherapy, 1 is pending enucleation and 1 abandoned before enucleation. The standard-risk group 69 had risk pathology and 76 had no risk factors; 125 had no events, 5 abandoned 11 relapsed/progressed and 2 died of toxicity. Of 95 high-risk group, 8 abandoned, 20 relapse/progressive, 6 had toxic deaths and 61 are alive at last follow-up (median time of 4 years). Of high risk group, 55 were unilateral, 82% are alive. At 7 years OS (abandonment-censored) was 95±0.02 and 79±0.04 for standard-risk and high-risk (p=0.008). Conclusion: AHOPCA addressed advanced intraocular disease with an innovative approach. In eyes with buphthalmos and patients with risk of abandonment, neo-adjuvant chemotherapy is effective, when followed by post-enucleation chemotherapy. This approach avoids ocular rupture and intensified therapy, and reduces refusal/abandonment rate. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors.

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Medulloblastoma: freedom from relapse longer than 8 years — a therapeutic cure?

Journal of Neurosurgery ◽

10.3171/jns.1991.75.4.0575 ◽

1991 ◽

Vol 75 (4) ◽

pp. 575-582 ◽

Cited By ~ 59

Author(s):

Mark G. Belza ◽

Sarah S. Donaldson ◽

Gary K. Steinberg ◽

Richard S. Cox ◽

Philip H. Cogen

Keyword(s):

Medical Center ◽

Survival Rates ◽

Adjunctive Treatment ◽

High Dose ◽

Content Type ◽

Significant Difference ◽

Long Term Follow Up ◽

Fine Print

✓ Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (≥ 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately.

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