scholarly journals Randomized Study of Pegasparagase (SS-PEG) and Calaspargase Pegol (SC-PEG) in Pediatric Patients with Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma: Results of DFCI ALL Consortium Protocol 11-001

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 175-175 ◽  
Author(s):  
Lewis B. Silverman ◽  
Traci M. Blonquist ◽  
Sarah K. Hunt ◽  
Samantha Kay-Green ◽  
Uma H. Athale ◽  
...  
Keyword(s):  
Single Dose ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Induction Dose ◽  
Post Induction ◽  
Significant Difference

Abstract Background: E.coli L-asparaginase (L-ASP) is an important component of treatment for childhood acute lymphoblastic leukemia (ALL), but the optimal preparation and dosing remain to be determined. Pegaspargase (SS-PEG) is a pegylated L-ASP formulation commonly used in frontline therapy. Calaspargase pegol (SC-PEG) is a novel formulation that uses the same ASP enzyme and PEG moiety as SS-PEG but a different linker molecule that is more hydrolytically stable, leading to a longer half-life. On Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols, patients (pts) typically receive a single dose SS-PEG during induction, and then 15 doses every 2-weeks (wks) during post-induction in order to maintain therapeutic serum asparaginase activity (SAA), defined as ≥ 0.1 IU/mL, for 30 consecutive wks. We hypothesized that SC-PEG could be administered less frequently than SS-PEG during post-induction therapy with a similar SAA and toxicity profile. Methods: Between 2012-2015, pts aged 1-21 years with newly diagnosed ALL or lymphoblastic lymphoma (LL) were eligible to enroll on DFCI ALL Consortium Protocol 11-001. Pts were randomized at study entry to receive either SS-PEG (N=120) or SC-PEG (N=119), each given intravenously (IV) at a dose of 2500 IU/m2. Both groups received a single dose during multi-agent remission induction. Post-induction, pts assigned to SS-PEG received 15 doses every 2-wks and those assigned to SC-PEG received 10 doses every 3-wks along with other risk-stratified chemotherapy. Serum samples were obtained 4, 11, 18 and 25 days after the induction dose to determine SAA and prior to each post-induction dose (2 wks after each SS-PEG and 3 wks after each SC-PEG dose) to determine nadir SAA (NSAA) by a validated biochemical assay. Pts were switched to Erwinia asparaginase for Grade 2 or higher allergy or for silent inactivation (defined as 2 consecutive non-detectable NSAA). Asparaginase was permanently discontinued for pancreatitis and held for thrombosis (but re-started once the clot improved). End-induction minimal residual disease (MRD) was assessed in ALL pts by IGH/TCRPCR assay, with low MRD defined as < 0.001. Results: 239 eligible pts were enrolled (230 ALL and 9 LL). There were no significant differences in presenting characteristics between randomized arms. SAA during induction and NSAA during post-induction are displayed in Figure 1. SAA was similar for the two preparations at 4, 11 and 18 days after the induction dose, with SAA ≥ 0.1 IU/mL in ≥ 95% of pts at these time points on both arms. 25 days after the induction dose, SAA was higher with SC-PEG (median 0.298 IU/mL vs 0.056 for SS-PEG), with significantly more pts on SC-PEG arm with SAA ≥ 0.1 IU/mL (88% vs 15%, p<0.0001). Post-induction NSAA was similar between arms, with median NSAA ≥ 1.0 IU/mL (10-times higher than goal NSAA) at 7, 13, 19 and 25 wks after beginning the 30-wk post-induction asparaginase treatment. NSAA was ≥ 0.1 IU/mL in ≥ 98% of pts on both arms at each time point. Two pts on the SC-PEG arm (1.7%) and none on the SS-PEG arm met criteria for silent inactivation. There was no significant difference in rates of ASP-related allergy (p=1.00), pancreatitis (p=1.00), thrombosis (p=0.22) or infections (p=0.86) during induction or post-induction treatment (Table 1). Of 230 evaluable pts, 97% achieved CR, with no difference in proportion of pts with low end-induction MRD by randomized arm (91% SC-PEG vs 90% SS-PEG, p=1.00). Conclusion: During remission induction, a single dose of SC-PEG (2500 IU/m2) leads to more sustained SAA without excess toxicity or significant difference in the proportion of pts with low end-induction MRD. During post-induction therapy, SC-PEG can be given less frequently (every 3-wks) than SS-PEG (every 2-wks) with similar NSAA and toxicity. The high NSAA observed during post-induction therapy with each preparation suggests that a longer dosing interval and/or reduced dose may be feasible while still maintaining NSAA ≥ 0.1 IU/mL. Longer follow-up is necessary to determine event-free survival by randomized arm. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effectiveness of Dexamethasone compared with Prednisolone in Induction Therapy of Childhood Acute Lymphoblastic Leukemia

2016 ◽  
Vol 6 (1) ◽  
pp. 3-9
Author(s):  
Tofazzal Hossain ◽  
MA Mannan ◽  
Shamsoon Nahar ◽  
AKM Amirul Morshed ◽  
Shahnoor Islam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Group A ◽  
Bone Marrow Study ◽  
Group B

Background: Corticosteroids are an essential component of treatment for acute lymphoblastic leukemia (ALL). Prednisolone is the most commonly used steroid. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of central nervous system compared with prednisolone.Objectives: To determine the effect of dexamethasone and prednisolone and to compare them in induction therapy of ALL in Children.Material & Methods: A total of 60 newly diagnosed cases of ALL confirmed by bone marrow study, children of either sex with age >1 year were included in this study. Variables studied were age, sex, presenting features, neutrophil count, blast cell count, platelet count, bone marrow status at diagnosis, on D15 & D29 of induction and side effects.Results: Mean age of the patients of group A was 6.28 years & that of group B was 7.2 years. Out of all patients of group A 19 (63.3%) were male and 11 (36.7%) were female. In group B 21 (70.0%) patients were male and rests 9 (30.3%) were female. No statistically significant difference was observed in both groups in terms of age, sex & presenting features. After induction significant difference was observed in liver & spleen size at day 7 and day 15. All patients of both groups had M3 marrow status at diagnosis. Overall, in group A 93.3% patients achieved M1 marrow status (fewer than 5% blasts) and 6.7% had M2 marrow status (5-25% blasts) at day 15 of induction. On the other side 66.7% patients of group B achieved M1 status and 33.3% M2 status at day 15. Statistically significant difference was observed between groups on day 15 in term of achieved marrow status (p<0.05). No statistically significant difference was observed between groups in term of infection in difference days of induction. On day 16 of induction maximum incidence of infection was observed in both groups.Conclusion: Dexamethasone may be an effective alternative option to prednisolone for the treatment of acute lymphoblastic leukemia in children.J. Paediatr. Surg. Bangladesh 6(1): 3-9, 2015 (Jan)

scholarly journals Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia

Blood ◽  
2010 ◽  
Vol 115 (7) ◽  
pp. 1351-1353 ◽  
Author(s):  
Lewis B. Silverman ◽  
Jeffrey G. Supko ◽  
Kristen E. Stevenson ◽  
Christina Woodward ◽  
Lynda M. Vrooman ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Enzyme Activity ◽  
Single Dose ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
The Past ◽  
Dana Farber Cancer Institute ◽  
Asparaginase Activity

Abstract Over the past several decades, L-asparaginase, an important component of therapy for acute lymphoblastic leukemia (ALL), has typically been administered intramuscularly rather than intravenously in North America because of concerns regarding anaphylaxis. We evaluated the feasibility of giving polyethylene glycosylated (PEG)–asparaginase, the polyethylene glycol conjugate of Escherichia coli L-asparaginase, by intravenous infusion in children with ALL. Between 2005 and 2007, 197 patients (age, 1-17 years) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-01 and received a single dose of intravenous PEG-asparaginase (2500 IU/m2) over 1 hour during remission induction. Serum asparaginase activity more than 0.1 IU/mL was detected in 95%, 88%, and 7% of patients at 11, 18, and 25 days after dosing, respectively. Toxicities included allergy (1.5%), venous thrombosis (2%), and pancreatitis (4.6%). We conclude that intravenous administration of PEG-asparaginase is tolerable in children with ALL, and potentially therapeutic enzyme activity is maintained for at least 2 weeks after a single dose in most patients. This trial was registered at www.clinicaltrials.gov as #NCT00400946.

Intensification With Intermediate-Dose Intravenous Methotrexate Is Effective Therapy for Children With Lower-Risk B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study

2000 ◽  
Vol 18 (6) ◽  
pp. 1285-1294 ◽  
Author(s):  
Donald H. Mahoney ◽  
Jonathan J. Shuster ◽  
Ruprecht Nitschke ◽  
Stephen Lauer ◽  
C. Philip Steuber ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Effective Therapy ◽  
Remission Induction ◽  
Intrathecal Therapy ◽  
Continuation Therapy ◽  
Increased Risk ◽  
Significant Difference ◽  
Prevention Of Relapse

PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m2 plus IV MP 1,000 mg/m2 (regimen A) or IV MTX 1,000 mg/m2 alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years. RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen. CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.

Treatment of Adult T-ALL with a Pediatric Asparaginase-Intensive Protocol Results in Survival Benefit When Compared to Other Adult Based Protocols

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3956-3956
Author(s):  
Murtadha K. Al-Khabori ◽  
Mark Minden ◽  
Vikas Gupta ◽  
Aaron D. Schimmer ◽  
Andre C. Schuh ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Treatment Regimen ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Entire Group ◽  
Induction Phase ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

Abstract T cell acute lymphoblastic leukemia (T-ALL) accounts for 14–22% of adult ALL. No prospective comparisons between different chemotherapy protocols have been done. Since 2000 a modified DFCI protocol (Silverman et al, Blood2001;97:121–1218) has been used as standard treatment for all newly diagnosed patients with T-ALL at Princess Margaret Hospital (PMH). This protocol includes a remission induction phase, a CNS prophylaxis phase with intrathecal chemotherapy and 12 Gy cranial irradiation, a 30-week intensification phase including weekly asparaginase, and a 72-week maintenance phase. We compared outcomes using this regimen to previous results for all newly diagnosed T-ALL from 1990 – 2000 at PMH using the standard institutional protocol in use at the time. Between 1990–2000, 44 patients (Group 1) were treated with a variety of protocols, including 9203ALL PMH protocol (11 patients), L10 (2 pts), Protocol C (7 pts), HyperCVAD (15 pts) and ECOG E2993 (9 pts). From 2000–2007, 33 T-ALL patients were treated with modified DFCI protocol (Group 2). The median age for all patients was 31 years (range 14–69 years). There was no significant difference between the two groups with respect to age at diagnosis, presenting WBC (median or percent &gt; 100 ×109/L), CSF positivity, or cytogenetics. More patients from Group 1 underwent allogeneic stem cell transplantation (BMT) in CR-1 (54%) as compared to those in Group 2 (54% vs. 14%, P = 0.001), primarily due to a change in BMT policy in 2002. The median follow up was 23 months (range 1–161 months) for the entire group and 53 months (range 14–161 months) for the surviving patients. Sixty-nine patients (90%) achieved complete remission, and 37 patients have relapsed. The CR rates were not significantly different between the two groups. The 3-year failure-free survival (FFS) was significantly higher in Group 2 (DFCI protocol) as compared with Group 1 (other protocols) (89% vs. 27%, P = 0.0001). Multivariate analysis using Cox proportional hazard model showed only the treatment regimen received (DFCI vs. others) to have a statistically significant impact on FFS (P = 0.0001). The 3-year overall survival (OS) was significantly higher in the DFCI group compared to the group receiving the other protocols (81% vs. 45%, P = 0.0006). On multivariate analysis, only the treatment regimen received (P=0.001) and the CSF status (P=0.014) had a significant impact on OS; BMT did not have a significant impact on OS. When patients were censored at the time of transplant, the FFS and OS analyses still showed statistically significant benefit for patients treated on DFCI protocol (P = 0.0001 and 0.03, respectively). In summary, treatment outcomes have markedly improved from 2000 onward as compared to the previous decade. Although improvements in supportive care and reduced use of allogeneic BMT may have been factors, it is likely that the institution of the DFCI pediatric protocol was the primary factor in the improved outcome. These results support the use of such pediatric asparaginase-intensive pediatric protocols for adult T-ALL.

Infectious Central Venous Line Complications During Induction Therapy for Newly Diagnosed Acute Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4322-4322
Author(s):  
Rebecca Cook ◽  
Roger Berkow
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Wound Dehiscence ◽  
Newly Diagnosed ◽  
Central Venous ◽  
Central Lines ◽  
Picc Line

Abstract Abstract 4322 Introduction: Childhood acute leukemia treatment requires central venous lines (CVL) for instillation of chemotherapy and blood products. Ideally, a proper white cell count (WBC) and absolute neutrophil count (ANC) ensure proper healing of CVLs, but this is challenging in children with acute leukemia. We sought to investigate the CVL complication rate in newly diagnosed children with acute leukemia during their induction therapy, and determine if the degree of neutropenia at the time of CVL placement correlated with the number of CVLs lost due to infection, wound dehiscence, or thrombosis. Methods: We conducted a retrospective chart review of children diagnosed with leukemia between January 2007 and December 2009 and recorded leukemia type, WBC and ANC at diagnosis and at the time of CVL placement, the type of CVL placed (external line, subcutaneous port) or placement of peripherally inserted central (PICC) line. We recorded complications, including infection, line malfunction, wound dehiscence, and thrombosis within their induction therapy phase. Results: Ninety-five children were evaluable, including 68 children with precursor B acute lymphoblastic leukemia (pre B ALL), 19 with acute myelogenous leukemia (AML), and 8 with T-cell acute lymphoblastic leukemia (T cell ALL). Ninety-eight CVLs were placed in 94 children (1 child died of complications of APML before initiation of therapy). There were 77 subcutaneous ports and 21 external lines placed. Eleven patients received PICC lines for various reasons (ex – sedation risk due to large mediastinal mass or altered mental status due to leukocytosis, coagulopathy, refractory thrombocytopenia, previously placed PICC line at outside hospital). ANC at the time of CVL insertion was reviewed: ANC<500 in 39 central lines, 500–1000 in 29 central lines, and >1000 in 30 central lines. Only 1 central line was removed due to wound dehiscence in a child with T cell ALL, and 2 central lines were removed for cellulitis in children with pre B ALL, and all these patients had ANC<500 at the time of line insertion. Two of the 98 central lines developed an associated thrombosis (1 CVL associated extensive arm venous thrombus and 1 external line with small atrial thrombus at tip of catheter), as opposed to 2 of the 11 PICC lines placed (both extensive arm venous thrombi). Seventeen positive blood cultures occurred during the first month of induction (15 from central lines and 2 from PICC lines), and all infections cleared with antibiotics except for 1 patient with PICC-associated venous thrombosis and persistent MRSA bacteremia. One subcutaneous port had to be revised after 3 days due to deep insertion and difficultly accessing; this child had ANCs<500 during each surgery and healed without complications. Three external lines were removed due to malfunction (2 with ANC<500, 1 with ANC 500–1000 at time of insertion). Conclusions: Nearly 40% of CVLs were placed in times of severe neutropenia (ANC<500), and only 3 were lost due to cellulitis or wound dehiscence. No CVL was lost due to persistent bacteremia compared to 1 PICC line. There was an increased incidence of thrombosis in PICC lines (2 of 11 placed) compared to external lines or ports (2 of 98 lines placed). We failed to see an increased risk of infection due to degree of neutropenia at the time of CVL insertion. Disclosures: No relevant conflicts of interest to declare.

Pentoxifylline During Steroid Window At Induction To Remission Increases Apoptosis In Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2623-2623
Author(s):  
Oscar Gonzalez-Ramella ◽  
Jimenez-Lopez Xochiquetzatl ◽  
Sergio Gallegos-Castorena ◽  
Pablo Ortiz-Lazareno ◽  
Jose Manuel Lerma-Diaz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Cancer Cells ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Control Group ◽  
Induction Phase ◽  
Study Group ◽  
Significant Difference

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the most common cancer diagnostic in children, and it represents the second death cause in this population. Despite advances in the treatment of childhood ALL, there are small portion of patients whom still succumb to this disease. A reduced apoptosis in cells plays an important role in carcinogenesis. This phenomenon is an important component in the cytotoxicity induced by anticancer drugs. A currently challenge is the chemotherapy resistance of tumor cells, inhibiting the apoptosis induced by chemotherapy. Pentoxifylline, (PTX) has been studied for its role on increase of apoptosis on cancer cells by different pathways. Our group has reported its efficacy in vitro and ex vivo in increasing apoptosis induced by chemotherapy drugs such as adriamycin and cisplatin in fresh leukemic human cells, lymphoma murine models and cervical cancer cells. We conducted a phase 1 controlled randomized trial to evaluate the efficacy of adding PTX to the steroid window during the remission induction phase in new diagnosed children with ALL. Methods We included all children from both sexes from 9 months to 17 years old during October 2011 to December 2012. Patients were divided into 3 groups, the first one as a non-malignant control group (NL group) included children with a non-hematology disease in which bone marrow aspiration (BMA) was mandatory in order to reach the diagnosis. The second one, the ALL control group whom received prednisone (PRD group) for the steroid window at 40mg/m2/day PO from day -7 to day 0; and then the third one (PTX group), the study group which included children receiving the steroid phase with PRD as early described, plus PTX at 10mg/kg/day IV divided in 3 doses, at the same days as recommended in our treatment protocol (Total Therapy XV). For all 3 groups a BMA was performed at diagnosis, for PRD group as well as PTX group, a second BMA was also collected at day 0. Apoptosis was evaluated by means of Annexin V Apoptosis Detection Kit FITC/PI (eBioscience¨, San Diego, CA, USA) in 1×106 bone marrow mononuclear cells. We measured minimal residual disease (MRD) by flow cytometry at day 14 to demonstrate complete remission in leukemic patients. Statically analysis was performed by U Man Whitney. Results We enrolled 32 patients: 10 in NL group; 11 in PRD group; and 11 in PTX group. The median age of all groups was 6 years (range 9 months-17 years). In PRD group, patient 1 abandoned treatment after administration of day 0, nevertheless the second BMA sample was collected. Patient number 7 died at day 4 due to complications from tumor lysis syndrome. Consequently, in these patients we were not able to measure MRD and BM aspiration at day 14. Except one patient in PRD group, all achieved complete remission at day 14. We did not find any significant difference between NL group and PRD and PTX groups before intervention (U=32 p=0.7; U=28.5 p=0.48 respectively). There was no significant difference between treatment groups before intervention (U= 37 p=0.79). However, after treatment we found an important difference between PRD and PTX groups, we observed an increase in apoptosis in PTX group in comparison with PRD group (U=17.5 p=0.04). There were no adverse effects during treatment. Conclusions The present study is the first one that shows the efficacy of PTX in increasing apoptosis induced by PRD in new ALL diagnosed children, whom have not received any treatment yet. This might be helpful, not only in patients with relapse, but to increase the overall cure rate in ALL. Further studies are needed to prove this hypothesis. With this objective, our study group is already planning a second trial were PTX will be given during all remission induction phase. Experimental reports strongly suggest that PTX induces inhibition of the transcription factor NF-ĸB, by inhibiting survival gens and facilitating apoptosis. To prove it, we are currently processing these patients' samples to know their genetic expression. Disclosures: No relevant conflicts of interest to declare.

Experience With BFM 95 Pediatric Regimen In Adult ACUTE Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5015-5015 ◽  
Author(s):  
Hakan Goker ◽  
Eylem Eliacik ◽  
Ayse Isik ◽  
Ibrahim C. Haznedaroglu ◽  
Nilgun Sayinalp ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Adult Acute Lymphoblastic Leukemia ◽  
High Doses ◽  
Dose Reductions

Abstract As treatment of adult acute lymphoblastic leukemia (ALL) is unsatisfactory compared to pediatric disease, there is ongoing interest in the treatment of adult ALL with pediatric regimens. In this context we started to use BFM 95 pediatric regimen (Blood 2008;111:4477) in relapsed adult ALL cases in April 2010 and extended this approach to newly diagnosed non-Burkitt and and non-Ph+ ALL cases aged < 30. Nineteen cases (15 male, 4 female; 11 de novo, 8 relapsed) have been treated during this period in Hacettepe University Med. Ctr. Hematology dept., Ankara, Turkey. Median (range) follow-up durations after BFM 95 regimen and after remission attainment were 4.3 months (1.6-31) and 4.25 (0.4-21.4). Median age was 22 (17-27) in de novo cases and 24 (20-46) in relapsed patients. Three out of 8 relapsed cases had relapsed after allogeneic stem cell transplantation (AlloSCT). Complete remission ratio was 18/19 (95%). One relapsed patient died during induction due to sepsis. The BFM 95 regimen primarily served as a remission induction protocol in relapsed cases. None of these cases completed the treatment protocol. They generally underwent AlloSCT (6 cases) or donor lymphocyte infusion (1 case) shortly after complete remission. Therefore these cases were censored at the time of transplantation in survival analyses. Two out of 11 newly diagnosed patients completed the protocol. In two other cases the treatment was stopped after 2 and 4 consolidation courses for AlloSCT. One de novo patient died in remission. The remaining six de novo cases are still on treatment. Sixteen patients were still alive by the time of last follow-up. Two deaths (during induction and consolidation) and 1 relapse were observed by this time. Median (95% confidence interval) estimated overall and disease-free survival durations were 31 months (not calculable) and 19.4 months (2.6-36.2), respectively. Grade 3-4 non-infectious toxicities were observed only in 5 (%26) patients during treatment. Liver dysfunction, pancreatitis, acute renal failure, and mucositis were occasionally observed. These significant toxicities were due to high doses of methotrexate (5 g/m2) and L-asparaginase (25 000/m2) which were used during early periods of this study. After adequate dose reductions these toxicities were not observed subsequently. Dose reduction for high dose dexamethasone (60 mg/m2) and CMV surveillance were also deemed necessary after one case of fatal CMV reactivation was observed during IIA consolidation protocol. In conclusion, BFM 95 regimen seems to be highly efficacious with a 95% CR rate in young adults. In order to reduce excess toxicities, appropriate dose reductions are necessary for high doses of methotrexate, L-asparaginase and dexamethasone which are applied during various steps of this regimen. However, longer follow-up and more patients and controlled studies are needed in order to reach firm conclusions. Disclosures: No relevant conflicts of interest to declare.

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