scholarly journals Ph-Negative Acute Lymphoblastic Leukemia (ALL) in Adolescents and Young Adults (AYA) Treated with Pediatric Argentine BFM-like Protocol: Real-Word Data on Prognostic Factors and Treatment

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4471-4471
Author(s):  
Luciana C Ferrari ◽  
María M Rivas ◽  
Isolda I Fernandez ◽  
Federico Sackmann ◽  
María J Mela Osorio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Young Adults ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Allogeneic Bone Marrow Transplantation ◽  
Adolescents And Young Adults ◽  
Prognostic Impact ◽  
Allogeneic Bone ◽  
Cns Involvement

Abstract Background: ALL in adults is considered a heterogeneous disease with poor prognosis. However, adolescents and young adults (AYA) display intermediate characteristics as compared with children. Risk groups and response predictors are essential to guide the treatment. Aims: The aim of this report was to evaluate the experience of Ph-negative ALL in AYA patients (pts) treated with the pediatric Argentine type-BFM protocol, assessing predictors of response in terms of overall survival (OS) and event-free survival (EFS). Methods: We performed a retrospective multicenter analysis of AYA pts diagnosed between 2013 to 2021, from 16 Argentine institutions who were treated following the pediatric Argentine type-BFM protocol. Response to prednisone (PR) at day(d) 8 (<1.0 and ≥1.0 x10 -9 blasts) in peripheral blood (PB) and complete remission (morphological remission -MCR- together with negative minimal residual disease -MRD- by flow cytometry) were evaluated. Events were defined as relapse, refractoriness or death. Chi2/Fisher's exact test, Kaplan-Meier / log rank test and Cox regression were used for statistical analysis. Results: One hundred and seventy-three patients similarly distributed among private and public institutions were analyzed. The median (Md) age was 22 years (15-40) with a male predominance (66%). At diagnosis, 23% presented central nervous system (CNS) involvement, 79.5% B and 20.5% T immunophenotype, 29% CD20 positive, 16% adverse cytogenetic/molecular findings and 29% no data. Ph-like screening was not routinely performed assessed only in 13% revealing two CRLF2 and one PDGFRB rearrangements. Twenty-one (12%) of pts underwent allogeneic bone marrow transplantation (Allo-HSCT) at 1 st line, 20 with MRD negative and 1 MRD positive at the time of the procedure.Of 171 pts, 155 (91%) achieved MCR, 12 (7%) were refractory, 3 (2%) died prior/during induction and 1 (0.6%) patient dropped out of treatment; 144 (84%) achieved negative MRD, 22 (13%) positive MRD and 5 (3%) were not evaluated. The Md to reach CR and MRD (-) was 33d (IQR 31-42) and 35d (IQR 32-73), respectively. With a Md follow-up of 16 months (1-79), 52 pts (30%) relapsed and 68 pts (39%) died. Early deaths at 3 months occurred in 8 (5%) pts, 5 related to treatment and 3 to disease. The Md OS and EFS were 58 and 34 months, respectively. Prognostic predictors analyzed were sex, white blood counts (WBC) at diagnosis (limit of 30 x10 -9/L), age (limit of 30 years), CNS involvement, cytogenetic/molecular findings, PR at d8, MRD in bone marrow (BM) at d15, 33 and 78. In the univariate analysis, response at d8, MRD at d15, 33 and 78 were useful to predict both OS and EFS, adding age and WBC in terms of OS. Similar results were obtained when patients who underwent Allo-HSCT were censored at the time of the procedure. (Table). In the multivariate analysis, positive MRD at d33 and d78 (and WBC in OS) maintained their independent adverse prognostic impact in relation to OS and EFS. Allo-HSCT showed benefits in pts with MRD >0.1% at d33 and >0.01% at d78 in terms of OS (d33: NR vs. 11 m, p =0.048, HR 0.3, 95%CI [0.1-0.9]; d78: NR vs. 8 m, p =0.009, HR 0.4, 95%CI [0.2-0.8]) and EFS (d33: NR vs. 6 m, p =0.022, HR 0.2, 95%CI [0.1-0.8]; d78: NR vs. 5 m, p =0.003, 0.1 HR, 95%CI [0.02-0.5]). The adverse risk of positive MRD at day 33 and 78 in terms of OS and EFS was overcome when pts were transplanted. Summary/Conclusion: The results show that positive MRD at d33 and 78 independently impacted on OS and EFS in our series and that Allo-HSCT overcame their adverse risk. Our data confirms the relevance of using pediatric protocols in AYA. On the other hand, the importance of prognostic tools in order to improve the outcome of AYA patients, reinforcing their inclusion in current guidelines. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Dose-Intensity Impacts On Survival of Adolescents and Young Adults with Acute Lymphoblastic Leukemia Treated in Adult Departments by a Pediatric Protocol (FRALLE 2000BT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3561-3561 ◽  
Author(s):  
Thomas Cluzeau ◽  
Nathalie Dhedin ◽  
Françoise Huguet ◽  
Emmanuel Raffoux ◽  
Sebastien Maury ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Dose Intensity ◽  
Adolescents And Young Adults ◽  
Induction Phase ◽  
Long Term Outcome ◽  
Response To Chemotherapy

Abstract Abstract 3561 Background: Adolescents (15–19y) with acute lymphoblastic leukemia (ALL) markedly benefit from pediatric rather than adult chemotherapy regimens, as highlighted by many retrospective studies (Boissel et al., JCO 2001). In young adults with ALL, there are now strong evidences that pediatric or pediatric-inspired protocols may also improve long-term outcome (Huguet et al., JCO 2009). However, whether care environment (adult vs pediatric unit) may impact this outcome remains an open issue. To address this question, we explored the outcome of adolescents and young adults (AYA, 15–29y) treated in adult hematology departments by the pediatric FRALLE 2000-BT protocol. Methods: From February 2001 to June 2011, 89 AYAs with Ph-negative ALL including 60 adolescents (15–19y) and 29 YAs (20–29y) were treated according to the pediatric FRALLE 2000-BT protocol in 13 French and Belgian adult hematology units (median follow-up, 5 years). After a prednisone prephase and a four-drug induction (prednisone, daunorubicin, vincristine and L-asparaginase), patients achieving CR received four 8-week phases of treatment: consolidation, 1st delayed intensification (DI), interphase, 2nd DI, and maintenance. According to FRALLE protocol recommendations, each phase should begin after hematological recovery of previous phase (ANC>1 G/L, Platelets>100 G/L). Twenty-five patients (18 adolescents and 7 YAs) underwent allogeneic transplantation after consolidation phase or 1stDI. Results: Apart age (median age, 18 vs 23y; p<.0001), adolescent and YAs cohorts had similar characteristics, including WBC, B/T lineage distribution, and high-risk karyotype (t(4;11)/MLL-AF4, hypodiploidy)), except for initial CNS involvement (1/60 vs 4/29 respectively, p=.02). Initial peripheral response to prednisone (PDN) at D7 and bone marrow response to chemotherapy at D21 were better in the adolescent subgroup, without reaching significance (slow PDN-responders: 30% vs 38%, p=.42; slow chemo-responders: 13% vs 21%, p=.37). Overall CR rate was 99% and did not differ between both cohorts (98% in adolescents, 100% in YAs). 5y-OS and 5y-EFS were estimated respectively at 66% and 61%. Despite similar CR rates, 5-year EFS was significantly shorter in adolescents than in YAs (47% vs 79%, p=.02). A non significant shorter 5y-OS was also observed in adolescents (58% vs 81%, p=.11). To explain this difference, we looked at dose-intensity disparities between both subgroups. During induction phase, no differences in drug cumulative doses were observed. To further explore potent difficulties to respect protocol schedules in younger patients, we compared intervals from induction D1 to start of different trial phases between both subgroups. In comparison to YAs, intervals from induction D1 to consolidation, 1st DI, 2nd DI and maintenance phases were progressively delayed in adolescents: 4 days for consolidation (p=.24), 6 days for 1st DI (p=.19), 9 days for 2nd DI (p=.005), and finally 25 days for maintenance phase (p=.0002). In univariate analysis, among age (adolescents vs YAs), B/T lineage, WBC, cytogenetics, and time to 1st DI, only age and time to 1st DI significantly affected EFS (p=.05 and p=.001 respectively). In bivariate analysis, age and time to 1st DI were identified as independent prognostic factors for EFS (p=.03 and p=.004, respectively). The same observation was done with interval time to 2ndDI. Conclusion: The outcome of AYAs treated in adult units with the pediatric FRALLE 2000 protocol is encouraging, particularly in YAs. The poorer outcome observed in adolescents may be related to increasing intervals from initial induction to the different phases of treatment. Prospective trials are required to register individual reasons that lead physicians and patients to progressively delay therapy. This study suggests that trial itself is not sufficient to improve the outcome in adolescents with cancer and that AYA programs are needed to explore the difficulties encountered by patients and care teams to adhere to therapy. Disclosures: No relevant conflicts of interest to declare.

Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.

1983 ◽  
Vol 1 (11) ◽  
pp. 669-676 ◽  
Author(s):  
K Jain ◽  
Z Arlin ◽  
R Mertelsmann ◽  
T Gee ◽  
S Kempin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Chronic Myelogenous Leukemia ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Leukocyte Antigen ◽  
Terminal Transferase

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d'Etude de la Greffe de Moelle Osseuse.

1989 ◽  
Vol 7 (6) ◽  
pp. 747-753 ◽  
Author(s):  
P Bordigoni ◽  
J P Vernant ◽  
G Souillet ◽  
E Gluckman ◽  
D Marininchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Disease Free

Thirty-two children ranging in age from 1.5 to 16 years with poor-prognosis acute lymphoblastic leukemia (ALL) were treated with myeloablative immunosuppressive therapy consisting of cyclophosphamide (CPM) and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) while in first complete remission (CR). The main reasons for assignment to BMT were WBC count greater than 100,000/microL, structural chromosomal abnormalities, and resistance to initial induction therapy. All children were transplanted with marrow from histocompatible siblings. Twenty-seven patients are alive in first CR for 7 to 82 months post-transplantation (median, 30 months). The actuarial disease-free survival rate is 84.4% (confidence interval, 7.2% to 29%) and the actuarial relapse rate is 3.5% (confidence interval, 0.9% to 13%). Four patients died of transplant-related complications, 16 developed low-grade acute graft-v-host disease (GVHD), and six developed chronic GVHD. The very low incidence of relapse (one of 28 long-term survivors) precluded the determination of the prognostic significance of the different poor-outcome features. Moreover, two infants treated with busulfan, CPM, and cytarabine (Ara-C) relapsed promptly in the marrow. In summary, as a means of providing long-term disease-free survival and possible cure, BMT should be considered for children with ALL presenting poor-prognostic features, particularly certain chromosomal translocations [t(4;11), t(9;22)], very high WBC counts, notably if associated with a non-T immunophenotype, and, perhaps, a poor response to initial therapy with corticosteroids (CS), or infants less than 6 months of age.

Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association.

1995 ◽  
Vol 13 (2) ◽  
pp. 352-358 ◽  
Author(s):  
C Uderzo ◽  
M G Valsecchi ◽  
A Bacigalupo ◽  
G Meloni ◽  
C Messina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Pediatric Hematology ◽  
First Relapse

PURPOSE To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized. PATIENTS AND METHODS All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors. RESULTS In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (> 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse). CONCLUSION Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.

Subtyping of erythrocyte phosphoglucomutase-1 as a genetic marker for bone-marrow engraftment and hematopoietic chimerism after allogeneic bone-marrow transplantation in a patient with acute lymphoblastic leukemia.

1988 ◽  
Vol 34 (12) ◽  
pp. 2586-2588 ◽  
Author(s):  
B Grahovac ◽  
B Labar ◽  
A Stavijenić
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Genetic Marker ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone Marrow ◽  
Allogeneic Bone ◽  
Marrow Graft

Abstract We report an effective follow-up of the establishment of bone-marrow function after an allogeneic bone-marrow transplantation in a patient with acute lymphoblastic leukemia, by means of a suitable genetic marker, phosphoglucomutase-1 (EC 5.4.2.2) isoenzyme. A patient with acute lymphoblastic leukemia received allogeneic bone-marrow graft from a sibling who was of the same sex and blood group, HLA-identical, and mixed-lymphocyte-culture nonreactive. To monitor the bone-marrow engraftment and the type and degree of chimerism established, we used a genetic marker, the phosphoglucomutase-1 isoenzyme system, to reveal the difference between the bone-marrow host and donor. We did phosphoglucomutase-1 isoenzyme subtyping of the host's and donor's erythrocytes before transplantation, and isoenzyme phenotyping of the host's erythrocytes during a year after transplantation. Establishment of bone-marrow graft function, a period of temporary mixed chimerism with a population of both host's and donor's erythrocytes, a period of the exclusive presence of donor's erythrocytes, and the resumed appearance of host's erythrocytes after eight months, with no signs of relapse of leukemia, were all observed by analysis of phenotypes. These isoenzymes served as a significant and practical genetic marker, which could be successfully used in studies on bone-marrow transplantation.

Analysis of the Clinical Features and the Prognosis of Acute Lymphoblastic Leukemia with Complex Chromosomal Aberrations

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4914-4914
Author(s):  
Xiujin Ye ◽  
Lixia Zhu ◽  
Li Li ◽  
Jie Zhang ◽  
Jingsong He ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Philadelphia Chromosome ◽  
Survival Outcome ◽  
Allogeneic Bone ◽  
Female Ratio ◽  
Laboratory Features

Abstract Abstract 4914 Background: Acute lympoblastic leukemia (ALL) with complex chromosomal aberrations (CCAs) which patients harboring three or more acquired chromosomal aberrations always have a poor outcome. Philadelphia chromosome–positive (Ph+) ALL is the largest genetically defined subtype in adult ALL with the most unfavorable prognosis. It is necessary to investigate the clinical and laboratory features of ALL patients with CCAs, analyze the distribution of Ph+ in these patients and assess the prognosis. Methods: In a retrospective follow-up study from 2005.1∼2011.6, 38 ALL patients with CCAs were investigated. All cases were diagnosed with morphological,immunological,cytogenetic classification and molecular biology. The karyotypes were interpreted according to the International System for Human Cytogenetic Nomenclature (ISCN). Clinical characteristics, laboratory features, treatment response and prognosis of ALL patients with CCAs were analyzed. Results: The study included 17 Ph+ ALL patients with an age range of 12 to 81 years (mean, 34.5 years) and a male to female ratio of 1:1. Ph+ ALL patients with CCAs were older than Ph- cases (P=0.096). The median survival time was 9.5 months (range, 1–44 months). The complete remission (CR) rate after two cycles of systemic chemotherapy was 53.6% (15/28) and the relapse rate was 53.3% (8/15). Ph+ ALL patients with CCAs showed a lower CR rate than Ph- cases. Eleven patients died during the follow-up period, six of them died within 2 months from the initial ALL diagnosis, and nine patients were failure to achieve CR. Three patients underwent allogeneic bone marrow transplantation (BMT): two of them presented Ph+ relapsed after 2 and 10 months, respectively. Using Kaplan-Meier survival analysis, we found the survival outcome of Ph+ ALL patients with CCAs is inferior to Ph- cases. Conclusion: Treatment outcomes of ALL patients with CCAs receiving chemotherapy or BMT are very poor. Ph+ as an unfavorable parameter influences on the CR rate and survival outcome. It is necessary to accumulate more clinical data to find innovative treatments that can improve the prognosis of this refractory leukemia. Disclosures: No relevant conflicts of interest to declare.

EZH2 Mutations Are Associated with Low Blast Percentage in Bone Marrow and −7/Del(7q) Karyotype in De Novo Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2544-2544
Author(s):  
Xiuli Wang ◽  
Haiping Dai ◽  
Qian WANG ◽  
Qinrong Wang ◽  
Yang Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Coding Region ◽  
Acute Myeloid

Abstract Abstract 2544 Somatic mutation of the EZH2 gene is seen in myelodisplastic syndrome, myelofibrosis, and chronic myelomonocytic leukemia patients. The prevalence and prognostic impact of somatic mutations of EZH2 in patients with acute myelogenous leukemia (AML) remains unknown. In this study, we sought to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo AML by PCR amplification of the entire coding region followed by direct bidirectional DNA sequencing. EZH2 mutations were identified in 13/714 (1.8%) of AML patients and occurred almost exclusively in males (11/13, P=0.033). In univariate analysis, the presence of EZH2 mutations was significantly associated with lower blast percentage (21–30%) in bone marrow (P=0.0001) and −7/del(7q) (P=0.025). There was no difference in the incidence of mutations in 13 genes, including ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. Complete remission, event-free survival or overall survival was similar between AML patients with and without EZH2 mutation (p>0.05). These results demonstrated EZH2 mutation as a recurrent genetic abnormality associated with lower blast percentage in BM and −7/del(7q) in de novo acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

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