Different Prognosis According to Subtype-Oriented Protocols in Elderly Patients with Acute Lymphoblastic Leukemia (ALL). Comparison of Three Prospective Parallel Trials from the Pethema Group

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3869-3869
Author(s):  
Josep-Maria Ribera ◽  
Olga Garcia ◽  
Pascual Fernandez ◽  
Pau Montesinos ◽  
Salut Brunet ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Early Death ◽  
Hematological Toxicity ◽  
P Value ◽  
Phase Ii Trials ◽  
Bulky Disease ◽  
Wbc Count

Abstract Background and objective ALL in elderly patients is associated with poor prognosis and many patients are not included in therapeutic trials. Consequently, the results of subtype-oriented protocols in elderly ALL are poorly known. We present the results of three prospective parallel subtype-oriented protocols from the Spanish PETHEMA group in ALL patients older than 55 years. Patients and Methods In 2008 three prospective phase II trials for ALL patients older than 55 yr with the Charlson Comorbidity Index ≤3 were activated: ALLOld07 (Ph-negative patients, NCT01366898, n=54), ALLOPh07 (Ph-positive patients, NCT01376427, n=48) and BURKIMAB08 (mature B-ALL, NCT00388193, n=18). The ALL0ld07 protocol included moderate-dose induction chemotherapy without genotoxic drugs, followed by consolidation and maintenance therapy for 2 years (Gökbuget et al, ASH 2008), the ALL OPh07 included imatinib and dexamethasone for induction followed by maintenance therapy with mercaptopurine and methotrexate and imatinib for 2 years, followed by imatinib for one additional year (Ribera et al, Br J Haematol 2012; 159: 485-488), and the BURKIMAB08 protocol included specific therapy for Burkitt’s lymphoma/leukemia together with rituximab (Ribera et al, Cancer 2013; 119:1660-8). The main outcomes (early death [ED], complete remission [CR], remission duration [RD] and overall survival [OS]) and toxicity (CTCAE v4.0) were compared. Results 40, 45 and 16 patients from ALLOld07, ALLOPh07 and BURKIMAB08, respectively, were evaluable for this study. Patients with mature B-ALL were more frequently male, with poorer general status, higher frequency of bulky disease and higher LDH serum levels, whereas no significant differences were observed on comparison of ALLOld07 and ALLOPh07 patients. The comparison of the main outcomes of the three trials is shown in Table 1. By multivariate analyses for RD the protocol and WBC count were identified as prognostic factors (BURKIMAB08 was considered as reference category), with HR [95%CI] of 6.8 [0.9-52.1], p=0.064, when compared with ALL Old07 and 3.1 [0.4-24.8], p=0.278 when compared with ALL OPh07, global p value=0.042, and HR [95%CI]: 1.004 [1-1.009], p=0.058 for the WBC count, respectively. The ECOG score was the only variable influencing OS (HR [95%CI]: 0.4 [0.2;0.8], p=0.003). Hematological toxicity in induction and consolidation as well as infections were significantly less frequent in ALLOPh07 than in other two trials, whereas renal toxicity was more frequent in BURKIMAB08. Conclusion Risk-adapted therapy in elderly patients with ALL was feasible and produced significantly different results in terms of CR duration, being the best for mature B-ALL and the poorest for Ph-negative ALL. Supported by the grants PI10/01417 from FIS and RD12-0036-0029 from Instituto Carlos III Disclosures: No relevant conflicts of interest to declare.

scholarly journals Early Deaths in Pediatric Acute Leukemia; A Challenge in Developing Countries

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5160-5160
Author(s):  
Hanafy Ahmed Hafez ◽  
Rawaa Solaiman ◽  
Dalia Bilal ◽  
Lobna m Shalaby
Keyword(s):  
Developing Countries ◽  
Acute Leukemia ◽  
Supportive Care ◽  
Death Rate ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Early Death ◽  
Response To Therapy ◽  
P Value

Abstract Background and objectives: The survival rates of children with acute leukemia is consistently improving, due to the lower relapse rates in addition to reducing treatment-related mortality, which is mainly a result of infectious causes. The aim of the study is to describe the incidence and risk factors associated with early deaths (first 42 days in treatment) among children with acute leukemia. Methods: This is a retrospective study included newly diagnosed patients with acute leukemia who presented to the National Cancer Institute, Cairo University between Jan. 2011 to Dec. 2013. Patients' data were collected from their files and analyzed for the total and early death rates and proposed causes of death. Results: The study included 370 patients, 253 with acute lymphoblastic leukemia (ALL), 100 with acute myeloid leukemia (AML) and 17 with mixed phenotypic acute leukemia (MPAL). The total death rate among the whole group was 40.5% (n=150) and induction death rate was 19.2% (n=71). AML was accompanied with higher rates of total and induction deaths as they were 58% and 25% respectively, compared to 33.6% and 17.4% in ALL. These early deaths were attributed mostly to infection 64.7% (n=46) and cerebrovascular accidents 18.3% (n=13). Early deaths were significantly higher in patients with age below 2 years old (p. value=0.008), and in those with poor response to therapy (p. value= 0.001). Using enhanced supportive care measures as better infection control, appropriate antibiotic guidelines and available intensive care unit during 2013 had significantly reduced the overall and induction mortality rates (27.8% and 13.8% respectively in 2013 versus 45% and 20.3% in 2011 and 49% and 25% in 2012). Conclusion: Induction deaths in pediatric acute leukemia remain a major challenge in developing countries and constitute an increasing fraction of all deaths. Accordingly, using a well equipped cancer centers with better supportive care guidelines is essential to further improve the survival in these group of patients. Key words: Acute Leukemia- Pediatrics- Early Death- Infection Disclosures No relevant conflicts of interest to declare.

Is Consolidation and/or Maintenance Treatment a Standard Therapy in Elderly AML in First Complete Remission?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2775-2775
Author(s):  
Elise Corre ◽  
Jean-Pierre Marie ◽  
Ollivier Legrand
Keyword(s):  
Complete Remission ◽  
Elderly Patients ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
P Value ◽  
Consolidation Therapy ◽  
Term Survival ◽  
Postremission Therapy ◽  
Wbc Count ◽  
First Complete Remission

Abstract The treatment of elderly patients with acute myeloid leukemia (AML) is very disappointing. Studies have established that if half of the intensivity treated patients achieve complete remission (CR), the high rate of relapse within the first year jeopardize the long term survival. No clearly effective postremission therapy had been established. Therefore we retrospective analyzed 141 elderly patients (>60 yo) in first CR, to evaluate the effectiveness of postremission therapy, consolidation (3+7or 2+5) and/or maintenance (low dose AraC). All patiens received a 3+7 induction therapy. In these 141 patients DFS and OS at 4 years are respectively 14%, and 19%. According to the clinical status of the patient after induction, 20 (14%) patients did not receive therapy after induction, 30 (21%) patients received only maintenance therapy, 53 (38%) patients received only consolidation therapy, and 38 patients (27%) received both consolidation and maintenance therapy. These 4 groups were stratified according to age (< >70 yo) and WBC (< or > 30 x 109/l) (See Tables). The outcome of these patients receiving or not post induction therapy is shown in these Tables. Patients DFS at 4 years OS at 4 years Consolidation No consolidation P value consolidation No consolidation P value Outcome of patients receiving or not consolidation therapy in 4 groups stratified according to age and WBC count < 70yo and WBC< 30x109/l 19% 13% p=0.01 27% 13% p=0.0074 <70yo and WBC>30x109/l 26% 0% p=0.08 38% 0% p=0.05 >70 yo and WBC < 30x109/l 0% 30% p=0.001 6% 30% p=0.01 >70 yo and WBC> 30x109/l 2% 0% NS 4% 0% NS In patients > 70 yo and WBC < 30 x 109/l patients who received consolidation have a poorer prognosis than patients who did not because the mortality in first complete remission (mortality during consolidation) was high (25% versus 0% respectively, P=0.01). Patients DFS at 4 years OS at 4 years Maintenance No Maintenance p value Maintenance No Maintenance P value Outcome of patients receiving or not maintenance therapy in 4 groups stratified according to age and WBC count <70yo and WBC<30x109/ 17% 20% NS 22% 25% NS <70 yo and WBC>30x109/l 23% 14% p=0.05 32% 23% NS >70 yo and WBC<30x109/l 25% 5% p=0.01 25% 5% p=0.008 >70 yo and WBC >30x109/l 2% 0% NS 4% 0% NS In conclusion, in patients < 70 yo consolidation ± maintenance therapy (for DFS in patients with > 30 x109/l) improves the outcome of these patients (DFS and OS). In patients > 70 yo and with WBC < 30 x109/l maintenance therapy without consolidation, improves outcome. In these later patients (> 70 yo and with WBC < 30 x 109/l) consolidation therapy decrease outcome. In patients > 70yo and with WBC > 30 x 109/l, both consolidation and/or maintenance therapy does not improve outcome.

scholarly journals Identification of Pharmacogenomic Single Nucleotide Polymorphism Variants As Contributors to Toxicity Phenotype in the Treatment of Acute Childhood Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Trisha Larkin ◽  
Abdelrahman H Elsayed ◽  
Roya Rafiee ◽  
Natasha Emanuel ◽  
Beate Greer ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Childhood Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Hematological Toxicity ◽  
P Value ◽  
Term Survival ◽  
Treatment Interruptions ◽  
Increased Risk ◽  
Gi Toxicity

Introduction: Despite more than 80% long-term survival in acute lymphoblastic leukemia (ALL), morbidity due to drug-related toxicities remains high. Treatment interruptions and omissions from these toxicities may affect survivorship outcomes and morbidities in pediatric cancer. Although multiple factors contribute to a patient's risk of toxicity pharmacogenetic factors have been shown to play critical roles. Genetic variation within genes involved in pharmacokinetic and pharmacodynamic pathways of chemotherapies can influence gene expression and/or activity resulting in inter-patient variation in drug levels and thus toxicity risk or therapeutic efficacy. Identification of SNPs of clinical relevance that are predictive of toxicity can allow clinicians to optimize therapy to manage toxicity phenotypes. Objective: The objective of this cross-sectional study was to explore pharmacogenomic biomarkers associated with clinically relevant toxicity phenotypes in children receiving ALL therapy. Methods: The protocol was approved by the University of Florida (UF) Institutional Review Board (IRB201802623). All participants provided informed consent. Patients ≤ 26 years of age with a diagnosis of de novo or secondary ALL and who had received induction and consolidation chemotherapy after May 2012 at UF were eligible for participation. Chart review was performed and CTCAE-graded toxicity data was abstracted for gastrointestinal (GI), neurological, and endocrine toxicities along with prolonged hospitalization (> 4 days) due to febrile neutropenia. Genomic DNA was obtained from peripheral blood. SNPs in candidate pharmacological genes in cytarabine, vincristine, methotrexate, daunorubicin/doxorubicin, mercaptopurine/thioguanine pathways were selected through literature search and PharmGKB database. Genotyping was performed using Sequenom-based based chemistry. SNPs with low call rate and minor allele frequency of <0.10 were filtered and 105 SNPs were tested for association with each toxicity endpoint using logistic regression models with additive, dominant, and recessive modes of inheritance. Odds ratio (OR) and 95% confidence interval were calculated for each test. SNPs with association P-value < 0.05 were considered significant. Results: Prevalence of toxicity and top genes with significant SNPs are summarized in Figure 1. SNP in a carbonyl reductase (CBR1) involved in anthracycline metabolism was associated with higher risk of GI toxicity (OR 2.49, p=0.016). Multiple SNPs in cytarabine pathway genes were associated with increased risk of GI toxicities (rs12067645 in CTPS1, rs11853372 in SLC28A1 and rs10916819 in CDA) whereas SNP in an influx transporter SLCO1B1, implicated in methotrexate uptake was associated with lower risk of GI toxicity (rs2291075, OR 0.224, p =0.017). Six SNPs were associated with higher incidence of hematological toxicity with most interesting SNP being rs12067645 in CTPS1, a gene involved in cytarabine metabolism (OR 5.89, p=0.026). rs1128503 in drug efflux transporter ABCB1, rs2228110 in ALDH3A1, and rs2853539 in TYMS were all associated with lower incidence of neurologic toxicities. rs4673 in CYBA (OR 3.76, p=0.015) associated with higher neurological toxicity. Of the 5 SNPs associated with endocrinopathies, 4 were associated with increased and one with reduced incidence of toxicity. Interestingly, 2 SNPs in cytarabine uptake transporter SLC29A1, rs507964 (OR 2.89, p=0.02) and rs324148 (OR 1.89, p=0.042) and one missense SNP rs1051266 in SLC19A implicated in methotrexate influx was predictive of prolonged hospitalizations from febrile neutropenia. Figure 1 highlights some of these results. Conclusion: In conclusion, we identified common SNPs in genes associated with pharmacology of most commonly used anti-leukemic agents that were predictive of interpatient variability in incidence of drug toxicity phenotypes in a pilot cohort of 51 patients with ALL. Though limited by sample size, our studies demonstrate exciting results with ongoing enrollment and analysis showing promise in developing a SNP based model for prediction of toxicity in pediatric patients. Our goal is to integrate SNPs into a toxicity score for each patient which, once validated in collaborative multi-site cohorts, will hold value when transitioned to the clinic for personalizing treatment regimens to achieve therapeutic benefit and minimize morbidities. Disclosures No relevant conflicts of interest to declare.

Comparison of Two Regimens for the Treatment of Elderly Patients with Acute Lymphoblastic Leukaemia (ALL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4490-4490 ◽  
Author(s):  
Massimo Offidani ◽  
Laura Corvatta ◽  
Lara Malerba ◽  
Monica Marconi ◽  
Massimo Catarini ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Lymphoblastic Leukemia ◽  
The Elderly ◽  
Infectious Complications ◽  
High Dose ◽  
Karyotypic Abnormality ◽  
Resistant Disease ◽  
B Lineage ◽  
Rare Malignancy ◽  
Wbc Count

Abstract Acute lymphoblastic leukemia (ALL) represents a rare malignancy in the elderly and few authors have specifically focused on the treatment of ALL in this setting. We recently published the results of a prospective phase II study comprising an induction therapy with vincristine, Daunoxome, cyclophosphamide and prednisone (VDXD) given to 15 patients aged ≥ 60 years. Here, we updated the results after enrolling 17 patients treated from 1999 to 2002 (median age 69 years, range 61–79) and we compared these with the results obtained in 17 elderly patients treated according to the GIMEMA ALL 0288 protocol from 1994 to 1998 (median age 70, range 61–76). Most of patients in both groups had B-lineage ALL and an initial WBC count less than 30 x 109/L. The most frequent karyotypic abnormality resulted the Ph which was detected in 4 (23%) and in 3 patients (17%) treated with 0288 and VDXD, respectively. BCR-ABL translocation was present in 45 % of patients treated with VDXD. Comorbidities were documented in 11 (65 %) patients treated with VDXD compared with 9 (58%) receiving 0288 regimen. With VDXD combination elderly ALL had a higher CR rate than with 0288 protocol (76.5% vs 41%; p=0.037) likely due to both lower induction mortality (17.5% vs 35%; p=0.028) and less resistant disease (6% vs 24%; p=0.025). Infectious complications rate was similar (64% vs 53%) but they were the primary cause of death in 2 and 5 patients receiving VDXD and 0288, respectively. Non-hematological side effects were comparable. Median DFS was similar and resulted 18 months and 20 months with 0288 and VDXD treatment, respectively. Median EFS was 3.9 and 12.8 months, respectively (p = 0.0486). Particularly, 1-year EFS resulted 35% in patients receiving 0288 treatment compared with 53% in those given VDXD. Median OS was 4.5 an 21 months in the first and in the latter group of patients (p = 0.0239) with a two-year OS of 29% in 0288 and 38% in VDXD group. Our results are encouraging and show that the administration of high-dose daunorubicin as liposomal compound in elderly ALL patients is not only feasible but also able to improve CR rate, EFS and OS without increase in toxicity.

Combined Analysis of Treatments for Pediatric T-ALL in KYCCSG Protocols, ALL-96 and ALL-02.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4102-4102
Author(s):  
Yasuhiro Okamoto ◽  
Yoshihisa Nagatoshi ◽  
Akinobu Matsuzaki ◽  
Aiko Suminoe ◽  
Hideki Nakayama ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
High Dose ◽  
Costal Margin ◽  
Hematopoietic Stem ◽  
Combined Analysis

Abstract Abstract 4102 Background Previously we reported the result of Kyushu-Yamaguchi Children's Cancer Study Group (KYCCSG) protocol, ALL-96, for pediatric acute lymphoblastic leukemia (ALL) (ASH meeting in 2005). The 7-year event-free survival (EFS) and overall survival (OS) rates were 72% (95% CI; 68 - 76 %) and 85 % (95% CI; 80 - 90 %), respectively. Following protocol, ALL-02, was aimed to assess the usefulness of polymerase chain reaction (PCR)-based minimal residual disease (MRD) in the same context as ALL-96 protocol. Purpose In this combined analysis, we analyzed the outcome and risk factors for relapse/survival in children with T-ALL who were treated with the ALL-96/ALL-02 protocols. Study Design and Treatment A total of 42 patients (22 of 218 in ALL-96 and 20 of 165 in ALL-02, 26 males and 16 females) with median age of 8 years (range 1 - 14) were treated. Patients were classified into 2 groups, standard risk (SR) and high risk (HR). HR patients had one of the followings: high white blood cell (WBC) counts more than 50,000/μl, T-cell immunophenotype, central nervous system (CNS) disease at diagnosis, organomegaly (hepatomegaly or splenomegaly more than 5 cm below costal margin), M2/3 marrow at day 15 of induction therapy. Both protocols consisted of induction, early intensification, consolidation, late intensification and maintenance therapy. Predonisolone (PSL), weekly vincristine (VCR), 4 doses of daunorubicin (DNR), 8 doses of L-asparaginase (L-asp) and 2 or 4 doses of intrathecal (IT) methotrexate (MTX) depending on the CNS status, were given during induction. In early intensification, DNR, cytarabine (CA), etoposide and 6-mercaptopurine (6-MP) were given. Consolidation consisted of intermediate dose of MTX, combination of cyclophosphamide(CPM), CA and 6-MP, and high dose CA. Late intensification similar to induction included 2 weeks of dexamethasone (DEX), weekly VCR, 2 doses of pirarubicin, single dose of CPM, 5 doses of L-asp and IT-MTX followed by combination of CA, 6-MP, IT-MTX along with 18 Gy cranial irradiation in 12 fractions. In ALL-96 protocol, patients were randomized to receive maintenance therapy of either combination of 6-MP/MTX and DEX/ VCR pulse (A-arm) or LSA2L2-type therapy (B-arm). In ALL-02 protocol, A-arm was chosen as a maintenance therapy based on result of ALL-96. No patient underwent hematopoietic stem cell transplantation (SCT) in 1st complete remission (CR). Results Median follow-up periods were 96 and 38 months in ALL-96 and ALL-02, respectively. Two patients were off-protocol before achieving CR because of toxicity and chromosome abnormality with t(4;11). Induction rate in 40 patients was 95%. All 14 events were relapses and TRM rate was 0%. Last event occurred at 40 months. The sites of relapse were isolated BM in 9, isolated testis in 2, isolated CNS in 1 and combined sites in 2. Nine died from disease progression and 2 died from toxicity after SCT in 2nd CR. The 4-year EFS and OS rates in all patients were 55 % (95 % CI; 39 – 71 %) and 71 % (95 % CI; 56 -86 %), respectively. EFS of ALL-96 and ALL-02 were 50 %[95 % CI; 29 -71 %]) and 65 % [95 % CI; 45 - 85 %]), respectively. OS of ALL-96 and ALL-02 were 59 % [95 % CI; 39 – 80 %]) and 90 % [95 % CI; 77 - 103 %]), respectively (p = 0.063). EFS of patients treated in A and B arm were 60 % [95 % CI; 41 -71 %]) and 55 % [95 % CI; 25 - 84 %]), respectively. None of age, sex, organomagaly, WBC, chromosomal abnormalities, CNS status, protocol, and maintenance arm was identified as a risk factor for relapse or survival. Two of 10 (ALL-96) and 3 of 4 (ALL-02) relapsed patients have survived with allogeneic SCT. Conclusion Although T-ALL patients received an intensified treatment including cranial radiation, the outcome was unsatisfactory. One possible explanation for better OS in ALL-02 protocol is that the majority of relapsed patients in ALL-02 were salvaged by SCT in 2nd CR. Disclosures: No relevant conflicts of interest to declare.

Childhood B-Precursor-ALL Presenting as Hepatitis - A Diagnostic and Therapeutic Challenge

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4331-4331
Author(s):  
Henriette Schneider ◽  
Ruediger Adam ◽  
Alexander Marx ◽  
Matthias Duerken
Keyword(s):  
Liver Enzymes ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Early Death ◽  
Infectious Hepatitis ◽  
Potential Hazard ◽  
Severe Hepatitis ◽  
Elevated Liver Enzymes ◽  
Piecemeal Necrosis ◽  
Clinical Dilemma

Abstract Abstract 4331 Liver involvement in childhood acute lymphoblastic leukemia (ALL) at presentation is common with hepatomegaly but severe impairment or hepatitis is rare with only 9 reported cases. The need to start anti-leukemic treatment despite the potential hazard of severe liver failure poses a clinical dilemma. We report a 6 year old girl who presented with jaundice, fever, vomiting and diarrhoea, cytopenia, hyperbilirubinemia of 5.7 mg/dl (direct 5.2), ASAT of 3389, ALAT of 2747 U/L, increased INR to 1.33, but normal ammonia. An acute common-ALL was diagnosed and serology, PCR-studies and cultures were negative for viruses causing hepatitis. Liver biopsy revealed diffuse hepatic blast infiltration, piecemeal necrosis and hepatocellular cholestasis without signs of infectious hepatitis. We treated the patient according to the ALL-BFM-2000-protocol without dose reductions and on day 8, hyperbilirubinemia had completely normalized and liver enzymes had significantly decreased. Further therapy was uneventful and the patient is alive and well 12 month after diagnosis, without any signs of hepatic dysfunction. Reviewing the literature on children with ALL presenting with hepatitis revealed 9 patients with a mean age of 8.8 years (range 4 to 15), female to male ratio of 2.0 and precursor B-cell immunophenotype in 8/9 patients. Patients had a mean bilirubin of 8.7 mg/dl (range 2 – 16.5), 3 had highly elevated transaminases above 2000 U/L, and two of them died initially. Another patient with moderately increased liver enzymes but hepatic encephalopathy needed transient hemofiltration, but survived. In none of the reported cases a viral organism has been identified and abnormal liver function normalized during chemotherapy in most of the patients. This indicates, that leukemia rather than infection was responsible for hepatitis. In conclusion, severe hepatitis in children with ALL is rare, seems to affect the older girl, and highly elevated liver enzymes are associated with early death. After infective organisms have been excluded, instant start of an effective induction therapy is required, even despite severe hepatitis, most probably caused by blast infiltration. 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.

Clofarabine Combinations in Adults with Refractory/Relapsed Acute Lymphoblastic Leukemia (ALL): A GRAALL Report

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2586-2586 ◽  
Author(s):  
Arnaud Pigneux ◽  
Mathieu Sauvezie ◽  
Norbert Vey ◽  
Emmanuel Raffoux ◽  
Ambroise Marcais ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Early Death ◽  
Bridge To Transplant ◽  
Grade 3

Abstract Abstract 2586 Even when intensively treated within pediatric-inspired protocols, about 25 to 30% of adults with ALL eventually relapse. With standard 4-drug or Hyper-CVAD salvages, post-relapse outcome remains very poor. Clofarabine is one of the new agents approved in US and EU to treat relapsing B-cell precursor (BCP) and T-cell ALL in children and young adults (up to 21 at initial diagnosis). In these patients, clofarabine is associated with a salvage rate around 30% when used as single agent. Combining clofarabine with conventional drugs in an intensive schedule may provide a chance to improve results in this difficult to treat population. Methods: Fifty-five patients were treated between March 2008 and February 2011. Thirty-seven patients received the VANDEVOL chemotherapy combining dexamethasone 10 mg/m2/12h day 1–5, mitoxantrone 8 mg/m2/d day 3–4, etoposide 150 mg/m2/d day 3–5, Peg-asparaginase 2.500 UI/m2 day 7, and Clofarabine 30 mg/m2/day day 1–5 and eighteen patients received the ENDEVOL chemotherapy combining cyclophosphamide 300 mg/m2/d day 1–3 and clofarabine 30 mg/m2/d day 1–5. Median age was 34 (19–67) and 53 (18–78) years in the VANDEVOL and ENDEVOL cohort, respectively. The proportion of first relapsing patients was 68% in the VANDEVOL cohort and 39% in the ENDEVOL cohort. Fifty patients had BCP-ALL (including 8 Ph+ ALL) and 5 patient had T-ALL. Results: Complete remission was achieved in 15/37 (41%) VANDEVOL patients and in 9/18 (50%) ENDEVOL patients. Early death rate was 5/37 (14%) in patients treated with VANDEVOL and 1/18 (6%) in patients treated by ENDEVOL. Grade 3–4 infectious, neurological, GI, and liver toxicities were observed in 22, 5, 5, and 11 VANDEVOL patients and in 10, 0, 0, and 2 ENDEVOL patients, respectively. Thirteen patients in the VANDEVOL group and three in the ENDEVOL group received subsequent allogeneic stem cell transplantation (overall transplant rate, 29%). After a median follow-up of 6 months, the median OS was 6.5 months. Conclusion: Combination of clofarabine with standard chemotherapy seems to be a promising and relatively safe approach to treat adult patients with refractory/relapsing ALL. This approach may be considered as a bridge to transplant in patients eligible for subsequent allogeneic stem cell transplantation. Updated data will be presented. The GRAALL will soon initiate a large multicenter prospective Phase II study using the VANDEVOL regimen. Disclosures: No relevant conflicts of interest to declare.

R-CHOP21 Vs R-CHOP14 in 950 Diffuse Large B-Cell Lymphoma Patients: Results of a Multicentre Retrospective Study Form Italian Lymphoma Foundation (FIL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1615-1615
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Maria Giuseppina Cabras ◽  
Luca Nassi ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Bulky Disease ◽  
Symptomatic Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1615 Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies have tested R-CHOP14 (C14). Aims: The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14 and to compare the efficacy of the therapy. Methods: All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent in 9 Italian Hematological Centers, were accrued. All patients treated with C14 used G-CSF as primary prophilaxis, and only elderly (over 70 years) patients treated with C21 used G-CSF as primary prophilaxis. Results: From january 2002 to june 2011, 950 pts were accrued, 643 pts were treated with C21 and 307 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age (<60 or >60 years) with more aged pts in C21 arm (p 0.001), bone marrow positivity and more than 3 lymph node stations involved that were higher in C14 arm (p: 0.05 and p: 0.001). After induction therapy 751 pts (79%) obtained a complete remission: 501/643 (78%) after C21 and 250/307 (81%) after C14. The remaining pts obtained partial response in 110 and 48 or no response in 32 and 9 respectively for C21 and C14. After a median period of observation of 38 months 104 pts relapsed (14%), 68 (65%) in the C21 arm and 36 (35%) in the C14 arm. After a median observation period of 3 years, considering the two therapies, C21 vs C14, no differences were reported in OS (Figure 1), PFS (Figure 2) and DFS: 80% vs 84%, 69% vs 71% and 54% vs 56% respectively. In univariate analysis OS was lower in older pts (azard ratio (ar): 2.57), IPI 2 (ar: 2.09), IPI 3 (ar: 4.36), IPI 4–5 (ar: 6.36), bulky disease (ar: 1.70), symptomatic disease (ar: 2.23). In multivariate analysis factors which mantained significantly worst prognosis were older age (ar: 1.35), IPI 2 (ar: 1.95), IPI 3 (ar: 3.76), IPI 4–5 (ar: 5.01) and bulky disease (ar: 1.43). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14. No differences in extra-hematological toxicity were observed. Secondary malignancies were reported: 7 in C21 and 3 in C14. After 3 years of median observation 188 pts are dead: 137 (73%) in C21 and 51 (27%) in C14 (not statistically significant, p:0.08). The large majority of pts are dead for disease progression or relapse. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population. Dose dense therapy did not affect OS or PFS also analysing sub group of pts. As expected a higher frequency of neutropenia was observed in C21 arm but did not translate in increasing infection rate. Further prospective randomized studies are needed to verify this preliminary observations. Disclosures: No relevant conflicts of interest to declare.

Feasibility of Electronic Directly Observed Therapy for Pediatric Leukemia Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3538-3538
Author(s):  
Adam Cohen ◽  
Lakshmanan Krishnamurti ◽  
Susan E. Creary
Keyword(s):  
Medication Adherence ◽  
Maintenance Therapy ◽  
Direct Observation ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Text Messages ◽  
Oral Steroid ◽  
Directly Observed Therapy ◽  
Pediatric Leukemia ◽  
Pediatric All

Abstract Abstract 3538 Introduction: Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, accounting for approximately 3000 cases per year. Although the cure rate of pediatric ALL exceeds 80% in developing countries, treatment usually lasts 2.5–3.5 years and consists of a prolonged maintenance therapy phase. This phase consists is a 20 to 32 month regimen of daily oral 6-mercaptopurine (6MP), weekly oral methotrexate, monthly intravenous vincristine, and monthly oral steroid pulses. It is estimated that non-adherence rates range from 10–40%, which increase the risk of relapse and have a negative impact on disease free survival. Prior studies show that directly observed therapy (DOT) is the most effective way to improve medication adherence, and it is widely used in anti-tuberculosis and anti-retroviral therapy. DOT is defined as a strategy for ensuring patient compliance with therapy, where a healthcare worker watches the patient swallow each dose of a prescribed medication. While DOT may be a successful strategy for pediatric ALL, cost, inconvenience, perceived intrusiveness, and stigma relating to frequent visits by healthcare workers make it less viable strategy for pediatric ALL patients. A modified version of DOT utilizes existing cellular and computer technology (Mobile DOT) to view patients taking their medications over the internet without the need for custom hardware or programming. This technique is being studied in the pediatric sickle cell population, and preliminary results show adherence rates of ≥90%. The primary aim of this study is to see if Mobile DOT is a feasible and acceptable way to monitor pediatric ALL patients' 6MP adherence. Methods: This was a 30-day pilot study. ALL patients in their first remission were recruited if they were between 1–22 years of age, were in maintenance therapy for ≥1 month, and had daily access to a phone or computer capable of recording and submitting videos to Mobile DOT. We instructed participants how to submit the videos and they received daily reminders alerts as text messages and emails to take their medication. As adherence measures, we used direct observation and self-reported adherence using the Moriskey Medication Adherence Surveys (MMAS-4). The MMAS-4 is a validated adherence survey on a scale of 0–4, where lower scores indicate higher adherence. We measured Mobile DOT participant satisfaction with a 12 question Likert scale survey at the end of the study. Participants received a small monetary compensation for completing surveys and if they achieved ≥90% adherence for the 30 days. Results: We approached 20 prospective participants and 11 enrolled. Two subjects withdrew from the study; one was withdrawn because he was instructed to stop 6MP therapy due to myelosuppression and the other was withdrawn because his software was incompatible with our system. At enrollment, mean MMAS-4 score was 0.8 (SD ± 1.2, range 0–3), suggesting good overall adherence. By the end of study, MMAS-4 score trended toward improvement to 0.3 (SD ± 0.5, range: 0–1). Of the participants with moderate adherence (scores 2–3, n=3), all improved to good adherence (score 0–1) at the end of the study. Mean adherence measured with direct observation was 27.0/30 (SD ± 2.5 range 23–30) or 90.0% (SD ± 8.3% range 76–100%). Survey data shows that most patients (n=5) found Mobile DOT and the alerts to be helpful. Also, most participants (n=8) found that Mobile DOT took less than five minutes each day and did not invade privacy. All participants agreed that Mobile DOT was easy to use. Conclusions: This study suggests that Mobile DOT is a feasible way to monitor medication adherence in pediatric ALL patients. In addition, we found pediatric ALL patients had high adherence rates and most found Mobile DOT to be acceptable. These results suggest that Mobile DOT may be an effective strategy to ensure adequate 6MP medication adherence in pediatric ALL throughout maintenance therapy. Disclosures: No relevant conflicts of interest to declare.

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