Influence of the fusion gene ETV6-RUNX1 in the prognosis of the Pediatric B- Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2515-2515
Author(s):  
Alejandro Contento-Gonzalo ◽  
Antonio Jimenez-Velazco ◽  
Alcala-Peña Magdalena ◽  
Manuel Barrios ◽  
Katie Hurst ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Rank Test ◽  
Prognostic Impact ◽  
Excellent Outcome ◽  
Log Rank Test ◽  
Significant Difference

Abstract Abstract 2515 INTRODUCTION AND OBJECTIVES: The ETV6-RUNX1 (TEL-AML1) rearrangement comes from the translocation of two chromosomes t(12;21)(p12;q22), and represents one of the most frequently detected anomalies (15–30%) in the B-precursor Acute Lymphoblastic Leukemia (B-ALL). It must be identified by polymerase chain reaction (PCR) or fluorescent in situ hybridization (FISH) methods, since this translocation is not detected by conventional cytogenetic techniques. The prognostic value of ETV6-RUNX1 is still a matter of controversy. Recently, the group of the St Jude Children's Hospital reported an excellent outcome in patients carrying the translocation, whereas the BMF group did not find any significant difference in the survival of ETV6-RUNX1 positive patients when compared to ETV6-RUNX1 negative. The aim of our study has been to determine the prognostic impact of the ETV6-RUNX1 rearrangement in patients diagnosed of B-ALL in our Hospital, after a long period of follow-up and with the same Spanish treatment protocols (from PETHEMA and SHOP groups). PATIENTS AND METHODS: All patients with B-ALL diagnosis from January 1997 to May 2011 were included in the study: in total, 114 patients with a mean of age of 6 ys (0.3–14). The type of leukemia was ALL common (83 patients), pro-B (17 patients), pre-B (13 patients) and mature (1 patient). All the children over 1 yr received treatment according to PETHEMA group protocols, adjusted to the risk. Children under 1 yr were treated following SHOP group protocols. Seventeen patients received an allogeneic transplantation. The main clinical features of the positive and negative patients for ETV6-RUNX1 are detailed in table 1. ETV6-RUNX1 assay was performed in our laboratory by RT-PCR, according to the European BIOMED project methodology. RESULTS: ETV6-RUNX1 was found in 31 of the 114 patients (27.2%). These patients showed a significantly higher frequency of myeloid antigens (p<0.001), and were always positive for CD10 (p=0.006). All cases of positive ETV6-RUNX1 were over 2 years old. No significant differences between positive and negative ETV6-RUNX1 were obtained when complete remissions (100 vs 80%), relapse (16 vs 20%) or deaths (10 vs 13%) were analyzed. Furthermore, estimation of disease free survival (DSF) at 14 ys for both groups were similar: 80 ± 8% for positive vs 66 ± 7% for negative (p=0.21, log-rank test). And the same happened for overall survival (OS): 87 ± 7% for positive vs 83 ± 5% for negative (p=0.4, log-rank test). DISCUSSION: In our series, including patients with B-ALL treated with similar protocols with long periods of follow-up, we could not find differences between positive and negative ETV6-RUNX1 patients. It is well known that the intensity of the chemotherapy regimen and the age of inclusion in different protocols may influence the prognosis. Therefore, at present, it is still a matter of discussion if previous reported differences in the B-ALL ETV6-RUNX1 positive group could be explained by a different stratification in risk groups or by different chemotherapy regimens. This work has been funded by a grant from AECC, Carmen Lavigne Prize 2010 Disclosures: No relevant conflicts of interest to declare.

Pediatric Therapy In Adult Acute Lymphoblastic Leukemia: Updated Experience of a Single Centre

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4338-4338
Author(s):  
Stefania Paolini ◽  
Sarah Parisi ◽  
Ilaria Iacobucci ◽  
Cristina Papayannidis ◽  
Maria Chiara Abbenante ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Hematological Toxicity ◽  
Induction Phase ◽  
Single Centre ◽  
Phase Ib ◽  
Small Series ◽  
Significant Difference

Abstract Abstract 4338 Background. Acute lymphoblastic leukemia (ALL) presents with different outcome in children and adults, with event-free-survival (EFS) rates of 70–80% and 30–40% at 5 years, respectively. This reflects both a different disease biology and different therapeutic approaches. Recently, results apparently improved in young adults/adolescents aged 15–21 years, with de novo ALL, when treated with pediatric intensive regimens rather than with typical adult regimens. Similarly, clinical studies are ongoing in older patients, toxicity related-therapy seeming the limiting issue. Aims. We report a single centre experience on adult ALL patients treated with an intensive pediatric-inspired schedule, designed to assess its tolerability and efficacy. Methods. From November 2007 to June 2010 seventeen ALL patients (M/F=12/5) were treated at our Center according to a modified AIEOP LAL2000 regimen. Treatment consisted of 7 days steroid pre-treatment, and four drugs 78-days induction (phase IA and phase IB) after which high risk (HR) patients were treated with three polychemotherapy blocks, while intermediate (IR) and standard risk (SR) patients went on 8-weeks consolidation and subsequent delayed intensification. Allo-SCT was planned for all patients with HLA-matched donor, as alternative to 2-years maintenance therapy. Median age was 31 years (range, 17–47). According to cytogenetic, response to steroid and minimal residual disease patients were classified into HR (n=7), IR (n=6) and SR (n=4). Results. 15/17 patients completed the induction phase IA, two being out for toxicity (grade IV infection and intestinal occlusion). Twelve (71%) obtained a complete remission (CR); three were refractory. However, one of them subsequently achieved CR after polychemotherapy blocks, for an overall response rate of 76% (13/17). Eleven patients then completed the 28-days induction IB. One patient is ongoing. Median induction duration was 92 days (range 82–136). Delays were mostly due to extra-hematological toxicity, the commonest being gastrointestinal (n=12), infective (n=7) and thrombotic (n=3). Delays were accumulated in both induction phases without significant difference between phase IA (median 18.5 days, range 4–37) and phase IB (median 17 days, range 9–66), despite an absolute number of moderate-severe AE superior in phase-IA versus phase-IB (12 vs 5). After induction, 4/12 patients already received consolidation therapy; 2/4 then received allo-SCT. The median duration of consolidation was 51 days (range 22–94). Conversely, 6/12 patients received polychemotherapy-blocks, one patient went directly on alloSCT and the remaining is ongoing. After polychemotherapy-blocks, five out six patients received allo-SCT. The median CR duration was 13 months (range 1+-42+); two patients relapsed, both after allo-SCT. With a median follow-up of 11 months (range 2–43) 11/17 (65%) patients are alive, 9 in CR (5 undergone allo-SCT). Six patients dead, three in CR for infectious complications, 3 for relapsed/refractory disease. Conclusions. Though in a small series, pediatric-like intensive chemotherapy seemed to be feasible in adult ALL. Extra-hematological toxicity, however, caused significant treatment delays during induction. Finally, the overall outcome appeared promising, though longer follow-up and larger populations are needed to draw definitive conclusions. Acknowledgments. BolognAIL, European LeukemiaNet, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO, Project of Integrated Program (PIO), Programma di Ricerca Regione – Università 2007–2009. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Poor Outcome of CRLF2 Rearranged Philadelphia Negative Acute Lymphoblastic Leukemia Adults Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5290-5290 ◽  
Author(s):  
Yasser H Elnahass ◽  
Omar A Fahmy ◽  
Mohamed Abdel Mooti Samra ◽  
Fatma A Elrefaey ◽  
Mahmoud T Bokhary ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Disease Free Survival ◽  
Bone Marrow Aspiration ◽  
Poor Outcome ◽  
Egyptian Patients ◽  
Diagnostic Work

Abstract BACKGROUND: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph'-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1 positive ALL and a poor outcome. Rearrangements of cytokine receptor like factor 2 (CRLF2) are identified in approximately 50% of Ph'-like and 10% of B-other ALL patients. AIM: To identify the incidence of CRLF2 rearrangements and the frequency of relapse in a cohort of B-other Precursor B-ALL adults Egyptian patients who were treated with conventional therapy at National Cancer Institute, Cairo University. METHODS: The routine diagnostic work-up at diagnosis included Bone marrow aspiration, immunophenotyping, karyotyping, fluorescent in situ hybridization (FISH) for BCR-ABL1 and KMT2A (MLL) and CRLF2 rearrangements (IGH-CRLF2 or P2RY8-CRLF2), and molecular analyses of BCR-ABL1 translocations. Patients within the age group 18-25 years received Total XV protocol while patients >25 years received Hoelzer's protocol. RESULTS: Forty patients were included (22 males, 18 females). Median age at diagnosis was 25 years (18 -65). Median TLC was 14.9 x109/L (1.1 - 201), median Hb was 9.9 gm/dl (5-12.9), median platelet count was 47 x 109/L (19-359) and median BM blasts count was 90% (30-100). CRLF2 rearrangement was detected in 4/40 (10%) patients. All CRLF2 positive patients (100%) relapsed at 6 months vs. 11/36 (30%) CRLF2 negative (p<0.001). At 6 months follow up, disease free survival (DFS) was 70% in CRLF2 negative patients vs. 0% in CRLF2 rearranged (p=0.04). At 1 year follow up, overall survival (OS) was 30 (75%) for CRLF2 negative vs. 0 (0%) for CRLF2 positive patients (p=0.01). CONCLUSION: CRLF2 rearrangements constitute a high risk independent prognostic factor in adult precursor B-ALL patients denoting a poor outcome and should be studied in ALL Ph' negative patients. Additional TKI therapy should be included for this category of patients in our protocols to improve outcome. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

First Results of the GRAAPH-2005 Study in younger Adult Patients with De Novo Philadelphia Positive Acute Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 12-12 ◽  
Author(s):  
Yves Chalandon ◽  
Xavier Thomas ◽  
Sandrine Hayette ◽  
Jean-Michel Cayuela ◽  
Claire Abbal ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
High Dose ◽  
Unrelated Donor ◽  
Molecular Response ◽  
Consolidation Chemotherapy ◽  
Significant Difference ◽  
Induction Regimen

Abstract The GRAAPH-2005 International study for adults with newly diagnosed chromosome Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) was designed to compare an imatinib-based induction regimen with an imatinib-HyperCVAD induction regimen and to evaluate the role of imatinib prior to stem cell transplantation (SCT). The protocol enrolled patients &gt; 18 years and &lt; 60 years. Among 118 enrolled patients from May 2006 onwards, 83 had a follow-up long enough to allow at least induction and consolidation evaluation. Median age was 42 years; 60% were male. A 7-day prephase steroid regimen (prednisone 60 mg/m2/day) allowed identification of the BCR/ABL transcript. In arm A (imatinib-based), imatinib 800 mg was given days 1–28, only combined with vincristine (2 mg at days 1, 8, 15, 22) and dexamethasone (40 mg at days 1–2, 8–9, 15–16, and 22–23). In arm B (imatinib-HyperCVAD), imatinib 800 mg was given days 1–14 of each course, combined with adriamycin (50 mg/m2 at day 4), cyclophosphamide (300 mg/m2/12h at day 1, 2, 3), vincristine (2 mg at days 4 and 11), and dexamethasone (40 mg at days 1–4 and 11–14) in the induction course, and combined with high-dose methotrexate (1 g/m2 at day 1) and high-dose cytarabine (3 g/m2/12h at days 2 and 3) in the salvage/consolidation course. Salvage/consolidation course was similar for patients initially following arm A. Four intrathecal infusions (methotrexate + cytarabine + methylprednisolone) were included within induction/consolidation courses. Complete hematological remission (CR) rate at the end of the two courses of induction/consolidation was 100% with arm A (42 patients of whom 2 after salvage course) and 95% with arm B (39/41 patients; all after induction course): overall 97.5% vs 70% in the pre imatinib era (LALA-94 trial). One patient died during the first course and 2 during the second course (of which 1 in CR after the induction course). Overall, median number of days to response was 37 (range, 28–136 days). Minimal residual disease (MRD) was centrally evaluated by quantitative RT-PCR at the end of induction (MRD-1) and at the end of salvage/consolidation chemotherapy (MRD-2). Molecular disease was undetectable in 11% at the time of MRD-1 and in 18% at the time of MRD-2, and at a level &lt; 0.1% in 40% at the time of MRD-1 and in 60% at that of MRD-2. Although this did not translate into significant difference in terms of survival, monitoring of MRD (&lt; 0.1%) documented that arm B was capable of inducing a deeper marked clearance of leukemic cells than arm A at the end of salvage/consolidation chemotherapy: 35% in arm A and 45% in armB (p = 0.3) for MRD-1, and 48% in arm A and 72% in arm B (p = 0.05) for MRD-2. After the two phases of induction/consolidation, patients received intensification by allogeneic SCT using related or unrelated donor stem cells or autologous SCT when a donor was not available and MRD &lt; 0.1%. In absence of potential SCT, they underwent repeated cycles of imatinib-HyperCVAD regimen. Of the 61 patients with enough follow-up after induction/consolidation courses, 52 (85%) actually received SCT: 41 allogeneic SCT (of which 25 from related- and 16 from unrelated-donor) and 11 autologous SCT. Overall survival (OS) was 62% at 2-year (68% and 54% in arm A and arm B, respectively; p = 0.3), which differ significantly from the 29% observed in the pre imatinib era (LALA-94 trial). Disease-free survival (DFS) was 43% at 2-year (54% and 32% in arm A and arm B, respectively; p = 0.7). After a median follow-up of 12.6 months (95% CI, 10.6–15 months), 18 relapses (22%) were observed. Eighteen patients have died after induction/consolidation phase: 8 patients with progressive disease and 10 patients in CR (1 from septic shock waiting for allogeneic SCT, and 9 from toxicity during allogeneic SCT). The preliminary data of this study suggest that an imatinib-based regimen induces a high rate of hematological CR, similar to a more intensive (HyperCVAD) regimen. However the rate of molecular response has a tendency to be lower with imatinib-based regimen. The combination of imatinib with chemotherapy allows a majority of patient to have consolidation with SCT.

scholarly journals Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2814-2822 ◽  
Author(s):  
CA Linker ◽  
LJ Levitt ◽  
M O'Donnell ◽  
SJ Forman ◽  
CA Ries
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Cell Phenotype ◽  
Free Survival ◽  
Prognostic Features ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

scholarly journals Interim Serum Soluble Interleukin-2 Receptor Levels Are Strongly Associated with Prognosis in Newly Diagnosis DLBCL Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4118-4118
Author(s):  
Haruya Okamoto ◽  
Akihiro Miyashita ◽  
Hiroaki Nagata ◽  
Yasuhiko Tsutsumi ◽  
Yuri Kamitsuji ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Interleukin 2 ◽  
B Cell Lymphoma ◽  
Clinical Variable ◽  
Rank Test ◽  
Prognostic Impact ◽  
Interleukin 2 Receptor ◽  
Log Rank Test ◽  
Soluble Interleukin 2 Receptor

<Background> Serum soluble interleukin-2 receptor (sIL2R) levels are often measured to evaluate the state of lymphoma. The serum sIL2R level at diagnosis has been reported to be correlated with the prognosis of diffuse large B cell lymphoma (DLBCL) patients treated with the R-CHOP regimen. However, it is unclear whether interim sIL2R levels are associated with prognosis in DLBCL. Here, we analyzed the prognostic impact of interim serum sIL2R levels in DLBCL. <Patients and Methods> We retrospectively examined data for DLBCL patients who started receiving chemotherapy at the Japanese Red Cross Society Kyoto Daini Hospital between January 2012 and December 2018. All of the patients received R-CHOP-like regimens (rituximab plus pirarubicin or adriamycin, cyclophosphamide, vincristine, and prednisolone). The interim sIL2R level (I-IL2R) was defined as the value measured after the third chemotherapy cycle. I-IL2R levels of >700 U/ml were regarded as positive. The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS). The unadjusted probabilities of PFS and OS were estimated using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. <Results> In total, 102 patients were enrolled. The patients' median age was 73.5 years (range, 35-88), 58 patients (56.9%) were male, and 52 (51.0%) had poor revised International Prognostic Index scores. The median follow-up time was 25.2 months (range, 3.7-88.6). Twenty-three patients (22.5%) were I-IL2R-positive (>700 U/ml). Univariate analysis revealed that I-IL2R-positivity was associated with a poor prognosis. The 3-y PFS rates of the I-IL2R-negative (<700 U/ml) and I- IL2R-positive (>700 U/ml) patients were 60.4% (95% confidence interval [95%CI], 46.2-71.9) and 37.5% (95%CI, 15.7-59.4; p<0.001, log-rank test), respectively, and their 3-y OS rates were 82.2% (95%CI, 69.7-89.9) and 37.4% (95%CI, 13.8-61.4; p<0.001, log-rank test), respectively. Multivariate analysis confirmed that the I-IL2R level is independently associated with prognosis. <Conclusion> The I-IL2R level of >700 U/ml patients had poor prognosis. The I-IL2R level can be used to predict the outcomes of DLBCL patients. IL2R levels should be measured during chemotherapy, and I-IL2R-positive patients could be targeted with high-dose or novel therapies. As this study was based on a retrospective analysis and involved a small cohort and a limited follow-up period, further studies are needed to confirm the prognostic impact of I-IL2R. Figure Disclosures No relevant conflicts of interest to declare.

Relapsed Childhood High Hyperdiploid Acute Lymphoblastic Leukemia: Genome-Wide Screening Reveals the Presence of Preleukemic Ancestral Clones and the Secondary Nature of Microdeletions and RTK-RAS Mutations.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2591-2591
Author(s):  
Josef Davidsson ◽  
Kajsa Paulsson ◽  
David Lindgren ◽  
Henrik Lilljebjörn ◽  
Tracy Chaplin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Structural Changes ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Snp Array ◽  
Prognostic Impact ◽  
Genetic Changes ◽  
Ras Mutations ◽  
Paired Samples

Abstract Abstract 2591 Poster Board II-567 Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% relapse. This makes it important to identify these patients already at diagnosis to ensure proper risk-stratification. To identify changes associated with relapse and ascertain the genetic evolution patterns, SNP array and mutation analyses of FLT3, KRAS, NRAS, and PTPN11 were performed on 11 paired diagnostic/relapse samples. The “triples trisomies” +4, +10, and +17 were detected in 64%, a frequency similar to the one generally observed at diagnosis, thus questioning their favorable prognostic impact. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P<0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. Based on the genetic relationship between the paired samples, three groups were delineated: 1) identical genetic changes at diagnosis and relapse (18%), 2) clonal evolution with all changes at diagnosis being present at relapse (18%), and 3) clonal evolution with some changes conserved, lost or gained (64%), suggesting the presence of a preleukemic clone. This ancestral clone was characterized by numerical changes only, with structural changes and RTK-RAS mutations being secondary to the high hyperdiploid pattern and perhaps necessary for overt leukemia. Disclosures: No relevant conflicts of interest to declare.

Outcome of Relapse After Allogeneic Transplantation for Childhood Acute Lymphoblastic Leukemia In Complete Remission. A Study of the Pediatric Diseases and Acute Leukemia Working Parties of the EBMT Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1291-1291
Author(s):  
Adriana Balduzzi ◽  
Myriam Labopin ◽  
Vanderson Rocha ◽  
Nabila Elarouci ◽  
Giorgio Dini ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Prognostic Impact ◽  
Dismal Prognosis ◽  
B Lineage ◽  
Donor Lymphocyte Infusions

Abstract Abstract 1291 Introduction. Childhood acute lymphoblastic leukemia (ALL) relapse occurring after hematopoietic cell transplantation (HCT) has a very dismal prognosis. Its treatment is still controversial and ranges from palliative treatment or chemotherapy to donor lymphocyte infusions, second transplant or experimental approaches. Objectives. The aim of this study is to assess the actual outcome in a pediatric population. The primary endpoint of this study is the 2-year probability of survival of children with ALL relapsing after allogeneic HCT; the secondary endpoint is the relationship between outcome and time of relapse after transplant, for which the following categories were considered: <3, 3–6, 6–12, > 12 months. Patients. Patients younger than 18 years of age undergoing first HCT from any allogeneic donor for ALL in first (CR1) or second (CR2) remission between January 1st 1998 and December 31st 2007 reported to the EBMT were eligible for the study. Results. Out of 3628 transplanted children with ALL reported to the EBMT, 836 (median age 9 years, male 66%) relapsed at a median of 6 months (range 1–67; 25th, 75th 4, 12 months) after HCT. The HCT was performed in CR1 (60%) or CR2 (40%) for a B-lineage (60%) or T- (13%) or unknown (27%) immunophenotype ALL, from an HLA-matched related (44%), unrelated (59%) or mismatched related (7%) donor, with marrow (61%), peripheral (28%) or umbilical (11%) stem cells. Out of 836, 81% died at a median of 2 months (25th,75th centiles:1,7) and 19% were reported as alive at last follow-up at a median of 22 months after relapse (range: 1–130). The 3-year probability of overall survival (3y-OS) was 14% (SE 1). As to immunophenotype, disease phase and donor type, 3y-OS was 15% (SE 2) in B-lineage and 8% (SE 3) in T-ALL, 18% (SE 2) in patients transplanted in CR1 and 11% (SE 6) in CR2 and 17% (SE 2) in patients transplanted from an HLA-identical sibling and 12% (SE 2) from any other donor. According to time of relapse after transplant, 3-year OS was 6% (SE 2), 10% (SE 2), 15% (SE 2) and 27% (SE 4) in those who relapsed in the first quarter, second quarter, second semester or after the first year, respectively. Donor lymphocyte infusions were reported for 7% and a second HCT for 16% of the 836 relapsed children. The probability of undergoing a second HCT within 1 year after relapse was 17% (SE 1); this probability was 6% for relapses occurring <6 months and 25% for later relapses. 3y-OS of those who underwent a second HCT was 32% (SE 5). Conclusions. The multivariate analyses confirmed the prognostic role of disease phase and immunophenotype, but not of the type of donor, assessed the strong prognostic impact of the time elapsed in CR after HCT before relapse, being earlier relapses at worse outcome compared with later relapses, possibly due to the chance of undergoing a second HCT, which role per se was not statistically significant. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Bone Marrow B Lymphocyte Precursors (hematogones) Detection in 95 Acute Lymphoblastic Leukemia Cases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4791-4791 ◽  
Author(s):  
Sylvain P Chantepie ◽  
Audrey Emmanuelle Dugué ◽  
Patrice Chevallier ◽  
Aline Schmidt-Tanguy ◽  
Véronique Salaün ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Time Points ◽  
Number Of Patients

Abstract Abstract 4791 Acute lymphoblastic leukemia (ALL) multiparameter flow cytometry (MFC) study of bone marrow aspiration after chemotherapy is crucial for determining minimal residual disease (MRD). Hematogones (HGs) have to be distinguishing from leukemic cells in B-cell subtypes and could be quantify during follow-up. To date, the incidence of Hgs in ALL and their prognostic significance have not been investigated. The aim of this multicenter study was to quantify Hgs after chemotherapy in ALL adult patients and to define its prognostic value. We retrospectively analyzed the incidence of HGs in 95 ALL patients, 71 with B-ALL (75%), 24 (25%) with T-ALL in first line treatment. The median age was 37 years [8–71], 20% had t(9;22) cytogenetic abnormality, and 70% had abnormal karyotype. 4/5-color MFC analysis MRD and HGs were performed at different time point (TP) after diagnosis: TP1 (post-induction, day 45 [41–61], n=78), TP2 (post-consolidation, day 111 [94–144] 25, n=42), TP3 (post-intensification/before hematopoietic stem cell transplantation (HSCT), day 179 [125–268], n=58), TP4 (n=11), TP5 (n=17), TP6 (n=9) after a median of 33, 91 and 167 days after HSCT, respectively. A total of 39 patients (41%) relapsed with a median of 26 months [7.7–47.9]. Forty seven patients (50%) received an HSCT in a complete (98%) or partial remission (2%). At TP1, TP2, TP3, TP4, TP5, TP6, the median HGs [range] were as followed: 0.00 [0.00–6.90]%, 0.30 [0.00–11.2]%, 0.98 [0.00–33.00]%, 0.52 [0.00;23.00]%, 5.50 [0.00;25.00]%, 4.60 [0.00;34.00]%, 5.90 [0.32;11.80]%, respectively. Figure 1 showed the percentage of patients with negative MRD (Figure 1A) and detectable HGs (figure 1B) during the follow up of ALL patients. There is a progressive increase of the percentage of patients with detectable HGs during the time of treatment and follow-up. Interestingly, there was no correlation between age and HGs level while in physiological situation the HGs rate decreases with increasing age. There was a negative correlation between positive MRD and detectable HGs at TP1 (p=0.022) but not at TP3 (p=0.88). In univariate analysis positive MRD at P1 and P3, age (/10), the presence of t(9;22) and absence of HGs at TP3 (figure 2) were bad prognostic factors for relapse free-survival (RFS) and overall survival (OS). The presence of HGs at other different time of evaluation was not associated with a significant decrease of relapse or death. However, patients who had a negative MRD at TP1 and detectable HGs in the bone marrow at TP3 exhibited a better RFS and OS (p=0.018 and p=0.065 respectively). Patients who had negative MRD at TP3 and had detectable HGs at TP3 had also a better RFS and OS (p=0.007 and p=0.011, respectively) compared to patients with negative MRD at TP3 and without HGs (figure 3). In patients who had a positive MRD at TP1, detectable HGs at TP3 identified a subgroup of patient with favorable OS compared to patient with positive MRD at TP1 and without detectable HGs (p=0.072). These results should be taken with cautious because of the decreasing number of patients evaluated at different time points. However, HGs analysis could represent a new area of investigation in search of new prognostic factors in the context of adult ALL. Figure 1. Percentage of patients with (A) negative MRD and (B) detectable HGs at different time points after starting of treatment. Figure 1. Percentage of patients with (A) negative MRD and (B) detectable HGs at different time points after starting of treatment. Figure 2. Overall survival according to HGs status at TP3. Figure 2. Overall survival according to HGs status at TP3. Figure 3. Overall survival in patients with negative MRD at TP3 according to HGs status. Figure 3. Overall survival in patients with negative MRD at TP3 according to HGs status. Disclosures: No relevant conflicts of interest to declare.

Augmented Berlin-Frankfurt-Muenster Based Therapy For Young Adults With Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1400-1400 ◽  
Author(s):  
Michael E. Rytting ◽  
Deborah A. Thomas ◽  
Susan O'Brien ◽  
Kurt Schroeder ◽  
Rebecca Garris ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Philadelphia Chromosome ◽  
Significant Difference ◽  
Grade Iii

Abstract Pediatric-based therapy of acute lymphoblastic leukemia (ALL) has been proposed as superior treatment for teen-agers and young adults with ALL. Several trials report improved survival rates in young adult ALL patients (pts) when treated with pediatric-based regimens. Augmented Berlin-Frankfurt-Muenster (ABFM) treatment is effective treatment for ALL in adolescents up to age 21. In an attempt to improve cure rates in AYA pts with ALL, we administered ABFM therapy to pts age 12 to 40 in a prospective, single institution trial. Results were then retrospectively compared to the HYPER CVAD regimen, the historical adult ALL regimen used at our institution. 85 pts with de novo Philadelphia chromosome negative ALL have completed at least 6 months of therapy. There are 69 (81%) pts with pre-B ALL and 16 (18%) pts with T-cell ALL/lymphoma. The age range is 13-39 with a median of 21. The median WBC at diagnosis is WBC=14 thousand/microliter (range 0.4-494). 80/85 (94%) pts entered remission (<5% blasts on day 29 marrow morphology). 1 patient died during induction. 61(72%) pts attained remission at day 15 of induction. 29 (22%) did not have morphological remission by day 15 of induction. At the end of induction, 46(58%) pts were minimal residual disease (MRD) negative by flow cytometry (<0.01% blasts). 25(31%) were positive for MRD and 6(7%) were not available or equivocal. By approximately day 84 of treatment, 55(69%) pts were negative for MRD and 13(16%) were positive or suspicious. Toxicities encountered include severe allergy to PEG-asparaginase in 17 (20%) pts, thrombosis in 18 (21%), hyperbilirubinemia grade III-IV in 31 (36%), elevated ALT grade III-IV in 28 (33%), hypofibrinogen grade III-IV in 30 (35%), pancreatitis in 9(11%), and avascular necrosis in 9 (11%). Grade III-IV hepatic toxicity is frequent but resolves within two weeks in almost all pts. For the entire cohort, the estimated 3 year overall survival (OS) is 75% and 3 year complete remission duration (CRD) is 71%. In univariate analysis, negative MRD at day 29 was associated with improved OS and day 84 negative MRD was associated with improved CRD. The presenting WBC was associated with OS and CRD. On multivariate analysis, only WBC over 50k/microliter maintained significance for OS and CRD. In comparing ABFM to HYPER CVAD, there is no significant difference in OS or CRD between the two regimens (fig. 1 and 2). This lack of difference in OS and CRD persists when patients are stratified for age > or </= 21 years, for presenting WBC over 50 thousand, and for MRD at the end of induction. In our hands, pediatric based therapy has significant though tolerable toxicity. Outcomes in AYA pts are similar but not superior to results obtained with historical ALL therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reoperation rates for symptomatic nonunions in posterior cervical (subaxial) fusions with and without bone morphogenetic protein in a cohort of 1158 patients

2016 ◽  
Vol 24 (4) ◽  
pp. 556-564 ◽  
Author(s):  
Kern H. Guppy ◽  
Jessica Harris ◽  
Jason Chen ◽  
Elizabeth W. Paxton ◽  
Julie Alvarez ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Patient Characteristics ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Morphogenetic Protein ◽  
Significant Difference ◽  
Spinal Fusions ◽  
Reoperation Rates

OBJECTIVE Bone morphogenetic protein (BMP) was first approved in 2002 for use in single-level anterior lumbar fusions as an alternative to iliac crest grafts. Subsequent studies have concluded that BMP provides superior fusions rates and therefore reduces reoperations for nonunions. The purpose of this study was to determine the reoperation rates for symptomatic nonunions in posterior cervical (subaxial) spinal fusions with and without the use of BMP and to determine if the nonunion rates are statistically significantly different between the two groups. METHODS Between January 2009 and September 2013, the authors identified 1158 posterior cervical spinal fusion cases in the subaxial spine (C2–7) from a large spine registry (Kaiser Permanente). Patient characteristics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Reoperations for symptomatic nonunions were adjudicated via chart review. Logistic regression was conducted to produce estimates of odds ratios (OR) and 95% confidence intervals (CIs). Kaplan-Meier curves for the non-BMP and BMP groups were generated and compared using the log-rank test. RESULTS In this cohort there were 1158 patients (19.3% with BMP) with a median follow up of 1.7 years (interquartile range [IQR] 0.7–2.9 years) and median duration to operative nonunion of 0.63 years (IQR 0.44–1.57 years). Kaplan-Meier curves showed no significant difference in reoperation rates for nonunions using the log-rank test (p = 0.179). In a subset of patients with more than 1 year of follow-up, 788 patients were identified (22.5% with BMP) with a median follow-up duration of 2.5 years (IQR 1.7–3.4 years) and a median time to operative nonunion of 0.73 years (IQR 0.44–1.57 years). There was no statistically significant difference in the symptomatic operative nonunion rates for posterior cervical (subaxial) fusions with BMP compared with non-BMP (1.1% vs 0.7%; crude OR 1.73, 95% CI 0.32–9.55, p = 0.527) for more than 1 year of follow-up. CONCLUSIONS This study presents the largest series of patients using BMP in posterior cervical (subaxial) spinal fusions. Reoperation rates for symptomatic nonunions with more than 1 year of follow-up were found to be 1.1% with BMP and 0.7% without BMP. There was no significant difference in the reoperation rates for symptomatic nonunions with or without BMP.

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