scholarly journals Treatment Experience of Acute Lymphoblastic Leukemia with Hgm/LAL07 Regimen at Hospital General De Mexico

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4871-4871
Author(s):  
Christian Omar Ramos Peñafiel ◽  
Humberto Baldemar Castellanos Sinco ◽  
Efreen Montaño Figueroa ◽  
María Guadalupe Leon Gonzalez ◽  
Etta Rozen Fuller ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Overall Survival ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
The Impact

Abstract Introduction Acute lymphoblastic leukemia is a lymphoproliferative malignancy characterized by an uncontrolled growth of lymphoid progenitors of B or T lineage, who evade apoptosis and displace normal hematopoiesis. Based on the pediatric pre-induction steroid, the protocol assessed the impact ALL0288 GIMEMA 7 days pre-induction with steroids, complete remissions (CR). Similar to this study, our institutional protocol also considers the pre-induction with steroids, but unlike the Italian protocol fewer cases steroid responders and a lower rate of complete remissions were recorded. A 36 month follow-up overall survival was 32% The main objective of this study was to evaluate the results at 5 years of follow institutional protocol based on a pre-treatment with steroids HGMLAL07. Patients. We included patients diagnosed with acute lymphoblastic leukemia under morphological criteria French-American-British (FAB) and corroborated by flow cytometry. The criteria for complete remission was seen at 4 weeks of treatment (<5% blasts in bone marrow with normal number of leukocytes and platelets). Prophylaxis central nervous system was carried out by weekly and then monthly lumbar punctures to the maintenance stage. If express the BCR-ABL oncogene was added to treatment Imatinib 400mg PO every 24 hours you first 14 days of each cycle. Materials and methods. Study design. Retrospective cohort study of adult patients treated with institutional protocol HGMLAL07 carriers de novo acute lymphoid leukemia in the period from 2007 to 2015 in the Department of Hematology, General Hospital of Mexico. We excluded patients treated with another induction therapy and those of mixed lineage leukemia. General treatment. It was considered relapse if they had at any time monitoring the presence of more than 10% blasts in bone marrow or isolation in the cerebrospinal fluid. If u have HLA-matched donor, he referred to the area of stem cell transplantation. Statistic analysis. SPSS statistical software version 20.0 was used. Chi-Square test considered significant at p <0.05 (95% CI) was used to test hypothesis testing. Survival analysis was performed using the Kaplan-Meyer test for comparing groups for overall survival and disease-free survival test was used log-rank2. The COX regression model was used for the risk function between different risk variables Results. Of the 262 patients with LLA de novo, 255 patients met the inclusion criteria and were treated with institutional protocol HGMLAL07, 52.9% were male gender (n = 135) and 47.1% (n = 120) Gender female. The mean age was 31 years (range 16- 80 years), the average for older female compared with male (34 versus 29years, p = 0.001, 95% CI). The average of leukocytes at diagnosis was 56.1 x 10 (9) / L. Phenotypically, most were classified leukemia B-cell (95.3%, n = 243) and the remaining T lineage (4.7%, n = 12). Only 3.1% of cases expressed the oncogene BCRABL1 (n = 8). Finally concluding that 62.7% of cases were classified as high risk (n = 160) and 37.3% (n = 95) and normal risk. Response to induction therapy. Of the 255 patients who started the protocol remission induction in 1.6% of confirmed with CNS infiltration diagnosis (n = 4). The complete remission rate was around 82.7% (n = 211), registering an induction mortality 3.9% (n = 10). A total of 34 patients were considered refractory leukemia (n = 34), requiring a second line treatment. Among the variables that showed the impact of the failure to initial treatment (refractory or death) were the type of risk at diagnosis (p = 0.020) and white blood cell count> 30 x 10 (9) / L (p = 0.001). Mean neutrophil recovery was 28 days and the platelet recovery was at 32 days. The main cause of death was infectious processes, followed by central nervous system bleeding. Postremisión treatment and outcome Of the total patients, 51% (n = 130) presented relapse, the main site bone marrow, followed by infiltration of the central nervous system Prognostic factors that impacted on survival The median overall survival (OS) was 1053 days, with survival at 5 years of follow-up of 29%, overall survival at 5 years was influenced by the type of risk (p = 0.020, 95% CI). None of the risk factors impact on survival at one year. The disease-free survival was 11% at 5 years of follow-up, within the variables that impacted on the SLE, a leukocyte count> 30 (9) / L and age> 35 years directly impacted prognosis (p = 0.006 and p = 0.030, 95% CI respectively). Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433

Haematologica ◽  
2020 ◽  
Vol 106 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Glen Lew ◽  
Yichen Chen ◽  
Xiaomin Lu ◽  
Susan R. Rheingold ◽  
James A. Whitlock ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Central Nervous System Relapse ◽  
Oncology Group

Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children’s Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93.8 +/- 2.7% for patients with MRD <0.1%, vs. 53.7 +/- 7.8% and 60.6 +/- 7.8% for patients with MRD ≥0.1% (p<0.0001). Patients who received HCT vs. chemotherapy alone had an improved 3-year disease-free survival (77.5 +/- 6.2% vs. 66.9 +/- 4.5%, p=0.03) but not OS (81.5 +/- 5.8% for HCT vs. 85.8 +/- 3.4% for chemotherapy, p=0.46). Patients with early iCNS relapse fared poorly, with a 3-year EFS/OS of 41.4% +/- 9.2% and 51.7% +/- 9.3%, respectively. Infectious toxicities of the chemotherapy platform were significant. The AALL0433 chemotherapy platform is efficacious for late bone marrow relapse of B-ALL, but with significant toxicities. The MRD threshold of 0.1% at the end of Induction-1 was highly predictive of outcome. The optimal role for HCT for this patient population remains uncertain. This trial is registered at clinicaltrials.gov (NCT# 00381680).

scholarly journals Central nervous system relapses after bone marrow transplantation for acute lymphoblastic leukemia in remission

Cancer ◽  
1989 ◽  
Vol 64 (9) ◽  
pp. 1796-1804 ◽  
Author(s):  
Gérard Ganem ◽  
Mathieu Kuentz ◽  
FrançOise Bernaudin ◽  
Abdelkader Gharbi ◽  
Catherine Cordonnier ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia

The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase

Blood ◽  
2009 ◽  
Vol 114 (25) ◽  
pp. 5146-5151 ◽  
Author(s):  
Lesleigh S. Abbott ◽  
Mariana Deevska ◽  
Conrad V. Fernandez ◽  
David Dix ◽  
Victoria E. Price ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Health Centre ◽  
Expectant Management ◽  
Fresh Frozen Plasma ◽  
Fresh Frozen ◽  
The Impact ◽  
Frozen Plasma

Abstract Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.

scholarly journals Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. BFM (Berlin- Frankfurt-Munster) Relapse Study Group

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3468-3472 ◽  
Author(s):  
C Buhrer ◽  
R Hartmann ◽  
R Fengler ◽  
S Schober ◽  
I Arlt ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Multicenter Trial ◽  
Cranial Radiotherapy ◽  
The Difference ◽  
Multiagent Chemotherapy

Abstract Presymptomatic central nervous system (CNS) treatment in children with a late isolated first bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL) was based on intermediate-dose systemic and intrathecal (IT) methotrexate (MTX) in the multicenter trial, ALL-REZ BFM 85. Because this was associated with an excess of overt second CNS relapses, cranial radiotherapy (cRT) plus prolonged triple IT therapy with MTX, cytarabine, and prednisone was instituted during the course of the subsequent trial, ALL-REZ BFM 87. Results of children with or without cRT, but otherwise identical chemotherapy, are presented here. Between April 1985 and March 1990, 93 children with their first late isolated BM relapse of ALL were entered on protocols ALL-REZ BFM 85M and ALL-REZ BFM 87. An intensive 6-month phase of multiagent chemotherapy that included 8 courses of systemic MTX (1 g/m2) plus IT MTX was followed by 2 years of conventional maintenance therapy with daily 6-thioguanine and biweekly MTX. Children with bone marrow transplantation excluded, 73 were in complete remission at the end of intensive polychemotherapy, 40 of whom received fractionated cRT plus triple IT therapy during the following 6 months; 11 did not receive cRT but prolonged triple IT; 22 received neither cRT nor prolonged triple IT. Except for a higher percentage of children who had received cRT in front-line protocols (29 of 33 v 20 of 40), the patient groups without or with salvage cRT were comparable. Of 33 children without salvage cRT, 26 relapsed, compared with 21 of 40 who had received cRT (P < .05). The difference was solely attributable to second relapses with CNS involvement (10 of 33 v 1 of 40; P < .01). Estimated 6-year event- free survival rates were .18 for children without cRT and .46 for children with cRT (P < .01). In patients without cRT, no impact of prolonged IT therapy could be shown. The data suggest that second CNS prophylaxis with cRT and prolonged triple IT therapy in children with late isolated BM relapse of ALL is effective in preventing CNS relapses, in reducing the overall relapse rate, and in increasing the overall survival rate.

Intensification of Chemotherapeutic Regimens and Hematopoietic Stem Cell Transplantation Are Responsible for Improved Overall Survival in Adult Acute Lymphoblastic Leukemia in a Single Center Over the Last Forty Years

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4227-4227
Author(s):  
Estrella Carrillo ◽  
Nancy Rodriguez ◽  
Juan Francisco Dominguez ◽  
Jose Gonzalez ◽  
Jose Francisco Falantes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Male Gender ◽  
Hematopoietic Stem ◽  
System Involvement ◽  
The Impact

Abstract Abstract 4227 Background Acute lymphoblastic leukemia (ALL) of adults is an infrequent and heterogeneous disease according to presentation pattern, prognosis and treatment. It is widely assumed that age above 30 years, leukocytosis >25 ×109/L, central nervous system involvement and specific cytogenetic disorders such as t(9;22) or MLL rearrangement entail bad prognosis. There are controversial studies on the impact of intensification chemotherapy and hematopoietic stem cell transplantation (HSCT) on survival of these high-risk groups. Aims To identify biological, clinical and prognostic characteristics in adult ALL patients diagnosed and followed in a single center throughout 40 years as long as the impact on clinical outcome of different consecutive therapeutic approaches, including HSCT, in different periods. Patients and methods Throughout 1970 to 2011, 230 patients were prospectively registered and retrospectively analyzed. Most patients accomplishing pre-determined criteria received treatment according to PETHEMA or locally developed therapeutic protocols (including HSCT in relapse high-risk patients, since 1978). Critical variables at diagnosis such as age, gender, phenotype (from 1978), cytogenetic (from 1999), white blood cells count (WBC) and central nervous system involvement, were analyzed. Response to induction chemotherapy, relapse rate (RR) and 5 year overall survival (OS) were analyzed in the whole cohort and separately by decade when treatment protocols were different. The clinical impact of HSCT was analyzed on a subgroup of patients homogeneously treated since 1994. Statistical analysis was performed by mean of Chi-square and Kaplan Meier tests, as appropriate. Outcome Table 1 summarizes the presentation pattern and its prognostic value. At diagnosis features such male gender, age above 30 years, central nervous system involvement, leukocytosis >10×109/L, MLL rearrangement, t(9:22) and complex karyotype entailed a worse prognosis. For the whole cohort the 5 years OS was 30%. CR was achieved in 73% and the RR was 38%. 5 years OS has improved by decades: 11% in the 70s, 24% in the 80s, 30% in the 90s, and 41% in XXI century (p<0,01). Patients selected for intensive chemotherapeutic protocols achieved a similar CR rate in each decade (nearly 80%) while the RR decreased through the years (70s: 68%, 80s: 44%, 90: 42%, 00–11: 25%; p<0,01). Patients treated with chemotherapy plus HSCT achieved in 5 years (from 1994) an OS of 69% in comparison with the 30% obtained in those patients who only received chemotherapy (p<0,01). Conclusion Male gender, age above 30, WBC >10×10e9/L, t(9;22), MLL-rearrangement, complex karyotype and CNS involvement conferred poor prognosis in adult ALL. Intensification of chemotherapeutic regimens produced a progressive decrease in relapse rate, leading to an improvement in overall survival over the years. HSCT seems to partially overcome the poor prognosis related to high risk factors. Disclosures: Perez-Simón: Janssen-Cilag: Patents & Royalties.

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.

scholarly journals Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. BFM (Berlin- Frankfurt-Munster) Relapse Study Group

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3468-3472
Author(s):  
C Buhrer ◽  
R Hartmann ◽  
R Fengler ◽  
S Schober ◽  
I Arlt ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Multicenter Trial ◽  
Cranial Radiotherapy ◽  
The Difference ◽  
Multiagent Chemotherapy

Presymptomatic central nervous system (CNS) treatment in children with a late isolated first bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL) was based on intermediate-dose systemic and intrathecal (IT) methotrexate (MTX) in the multicenter trial, ALL-REZ BFM 85. Because this was associated with an excess of overt second CNS relapses, cranial radiotherapy (cRT) plus prolonged triple IT therapy with MTX, cytarabine, and prednisone was instituted during the course of the subsequent trial, ALL-REZ BFM 87. Results of children with or without cRT, but otherwise identical chemotherapy, are presented here. Between April 1985 and March 1990, 93 children with their first late isolated BM relapse of ALL were entered on protocols ALL-REZ BFM 85M and ALL-REZ BFM 87. An intensive 6-month phase of multiagent chemotherapy that included 8 courses of systemic MTX (1 g/m2) plus IT MTX was followed by 2 years of conventional maintenance therapy with daily 6-thioguanine and biweekly MTX. Children with bone marrow transplantation excluded, 73 were in complete remission at the end of intensive polychemotherapy, 40 of whom received fractionated cRT plus triple IT therapy during the following 6 months; 11 did not receive cRT but prolonged triple IT; 22 received neither cRT nor prolonged triple IT. Except for a higher percentage of children who had received cRT in front-line protocols (29 of 33 v 20 of 40), the patient groups without or with salvage cRT were comparable. Of 33 children without salvage cRT, 26 relapsed, compared with 21 of 40 who had received cRT (P < .05). The difference was solely attributable to second relapses with CNS involvement (10 of 33 v 1 of 40; P < .01). Estimated 6-year event- free survival rates were .18 for children without cRT and .46 for children with cRT (P < .01). In patients without cRT, no impact of prolonged IT therapy could be shown. The data suggest that second CNS prophylaxis with cRT and prolonged triple IT therapy in children with late isolated BM relapse of ALL is effective in preventing CNS relapses, in reducing the overall relapse rate, and in increasing the overall survival rate.

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