Result of childhood acute lymphoblastic leukemia protocol (INCTR) from a developing country

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20015-20015 ◽  
Author(s):  
D. Mukhopadhyay ◽  
P. Gupta ◽  
S. Mukhopadhyay ◽  
P. Chitalkar ◽  
S. D. Banavali ◽  
...  
Keyword(s):  
Developing Countries ◽  
Developing Country ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Asian Population ◽  
Remission Induction ◽  
Acute Lymphatic Leukemia ◽  
Metabolic Complications ◽  
Childhood All ◽  
Lymphatic Leukemia

20015 Background: Acute Lymphatic Leukemia in children is a curable disease in the range of 80–90 % in developed Countries by aggressive protocol like BFM, St. Judes’. In developing Countries like ours, patients can’t tolerate those aggressive protocol because of Socio- economic and nutritional factors. The less aggressive Protocol like INCTR (International Network for Cancer Treatment & Research) are suitable in developing Countries like ours. The aim of our study was to see outcome of childhood ALL patient with INCTR protocol and tolerability of the protocol in Indian-asian population. Methods: We treated 480 Children (age range 1–25 years, median age of 11 yrs) with INCTR Protocol at Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India, a tertiary cancer centre from Eastern India during period from April ’99 to Dec ’06. There was female preponderance in the study. Fever 283 (58.9%), lymphadenopathy 211 (43.9%) and haepatosplenomegaly 153 (31.8%) were the major clinical presentation. Forty-three (8.9%) patients were present with hyper Leukocytosis. C-ALL phenotype were the largest group though the incidence of the T-ALL were quite high (27.9%). Results: Remission induction were seen in 446 (92.9%) of the patient. In a follow-up period of 88 months (with an average of 54 months) the disease-free survival ( DFS) was 66.8% (321 patients) with an overall survival of 73.9% (355 patients). The isolated bone marrow relapse was seen in majority of the cases 40 (8.33%) and the major relapse was in maintenance and first 6 months of completion of therapy. The major cause of morbidity was infection 316 (65.8%) followed metabolic complications 81 (16.8%), hemorrhage 52 (10.8%), neurologic 10 (2.08%), hepatitis 6 (1.25%) and pancreatitis 5 (1.04%). The major cause of the mortality was infection 75%(360 patients) followed progressive disease 7.91% (38 patients) and Hemorrhage 5.83%( 28 patients). Conclusions: The data of acute lymphatic leukemia from a developing country is encouraging. The protocol was well tolerated by India- asian population. No significant financial relationships to disclose.

Result of adolescent acute lymphoblastic leukemia protocol (MCP 841) from a developing country

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10046-10046 ◽  
Author(s):  
A. Mukhopadhyay ◽  
P. Gupta ◽  
S. Mukhopadhyay ◽  
S. Dey ◽  
J. Basak ◽  
...  
Keyword(s):  
Developing Countries ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Developed Countries ◽  
Cancer Center ◽  
Remission Induction ◽  
Age Group ◽  
Acute Lymphatic Leukemia ◽  
Metabolic Complications ◽  
Lymphatic Leukemia

10046 Background: Acute Lymphatic Leukemia is a curable disease in the range of 80 - 90% in developed countries by aggressive protocol like BFM, St. Judes’ but result is much less in adolescence age group (60–70%). In developing countries like ours, patients can't tolerate that aggressive protocol because of socio-economic and nutritional factors. The less aggressive protocol like MCP841 is suitable in developing countries like ours. The aim of our study was to see outcome of adolescent ALL patient with protocol MCP 841 and tolerability of the protocol in Indian-Asian population. Methods: We treated 75 children with age range 13 - 18 years (median age of 15 yrs) with MCP 841 Protocol at Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India, a tertiary cancer center from Eastern India during the period of April 1999 to Dec 2007. There was female preponderance in the study. Fever 48 (64.0%), lymphadenopathy 35 (46.7%), and haepatosplenomegaly 28 (37.3%) were the major clinical presentation. Eight (10.7%) patients were present with hyper leukocytosis. T-ALL phenotype was the largest group though the incidence of the C-ALL was quite high 23 (30.7%). Results: Remission induction was seen in 65 (86.7%) of the patients. In a follow-up period of 24 - 88 months (with an average of 54 months) the disease-free survival ( DFS) was 42 (56%) patients with an overall survival of 46 (61.34%) patients. The isolated bone marrow relapse was seen in majority of the cases 28 (37.34%) and the major relapse was in maintenance and first 6 months of completion of therapy. The major cause of morbidity was infection 53 (70.7%) followed metabolic complications 16 (21.34%), pancreatitis 3 (4.0%), hemorrhage 10 (13.3%), neurologic 2 (2.7%), and hepatitis 1 (1.3%). The major cause of the mortality was infection 18% (24.0% patients) followed progressive disease 9 (12.0%) and hemorrhage 2 (2.7%). As compared to our all pediatric ALL group the outcome is much less and complications are much more. Conclusions: The data of acute lymphatic leukemia in adolescent is not satisfactory as compared to other pediatric patients. They also tolerate chemotheraphy badly. Therefore there is need for modified protocol for this age group. No significant financial relationships to disclose.

Lymphomatoid Granulomatosis in a Child with Acute Lymphatic Leukemia in Remission

1978 ◽  
Vol 87 (5_suppl) ◽  
pp. 5-10 ◽  
Author(s):  
Seymour R. Cohen ◽  
Stuart Siegel ◽  
Eva Heuser ◽  
Benjamin H. Landing ◽  
Susan Shen ◽  
...  
Keyword(s):  
Survival Rate ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
Lymphomatoid Granulomatosis ◽  
Unknown Etiology ◽  
Acute Lymphatic Leukemia ◽  
Clinical Onset ◽  
Lymphatic Leukemia ◽  
Trachea And Bronchi ◽  
Other Neoplasms

Lymphomatoid granulomatosis, a tumor-like process of unknown etiology, produced progressively destructive disease of the larynx, trachea and bronchi in an eight-year-old girl with acute lymphoblastic leukemia of five years duration. The leukemia had been in remission for 4½ years at the clinical onset of the lymphomatoid granulomatosis. Whether this occurrence suggests that lymphomatoid granulomatosis is a type of neoplasm, or is associated with immunologic depression, cannot be stated. Fortunately rare, and of poor prognosis, the disorder may become more frequent with improved survival rate of patients with leukemia and other neoplasms.

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 “SOCIOECONOMIC FACTORS AFFECTING SURVIVAL IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA FROM NORTH-EAST INDIA”

2020 ◽  
pp. 1-3
Author(s):  
Partha Sarathi Roy ◽  
Munlima Hazarika ◽  
Rakesh Kumar Mishra ◽  
BhargabJyoti Saikia ◽  
Gaurav Kumar
Keyword(s):  
Overall Survival ◽  
Developing Countries ◽  
Acute Lymphoblastic Leukemia ◽  
Socioeconomic Factors ◽  
Lymphoblastic Leukemia ◽  
Childhood All ◽  
Female Ratio ◽  
Risk Of Death ◽  
Lower Socioeconomic ◽  
Pediatric All

Acute lymphoblastic leukemia (ALL) is a highly curable childhood cancer with a survival rate of nearly 80% in developed countries but is around 45% in developing countries. This retrospective study analyzed the association between demographic and socioeconomic factors with survival in pediatric ALL. All confirmed cases of pediatric ALL (age <18 years) registered at Dr. B Borooah Cancer Institute between 2010 to 2017 were analyzed using data collected from hospital-based cancer registry and case records. Seventy-five confirmed cases of pediatrics ALL were eligible for the study. The median age of presentation was six years with a male: female ratio 1.9:1. Overall survival at 4-years was 43.8%, with a median survival of 25 months. A trend for higher 4-year overall survival was seen in female children (54.1% versus 37.9%, p=0.097). Patients from rural areas (44% versus 39.5%, p=0.308), with higher maternal education (83.3% versus 41.1%, p=0.161) and patients who did not abandon treatment (49.1% versus 31.2%, p=0.497) had better survival, but the differences were not significant. Four years overall survival in upper-middle, lower-middle, upper-lower, and lower class were 85.7%, 74.9%, 38.1%, and 7.7% respectively (upper-middleversus lower socioeconomic class, p=0.0001).Multivariate analyses confirmed a statistically significant relationship between socioeconomic status and survival, with the upper-middle group had a 90% decreased risk of death compared to the lower socioeconomic group. There is an urgent need for a proper definition of the problems of childhood ALL to introduce appropriate policies for improving survival in developing countries.

scholarly journals Case Report: A rare association between SLE and Acute Lymphatic Leukemia

2018 ◽  
Vol 1 (3) ◽  
pp. 01-02
Author(s):  
P.K. Sasidharan
Keyword(s):  
Case Report ◽  
Acute Lymphoblastic Leukemia ◽  
Past History ◽  
Lymphoblastic Leukemia ◽  
Acute Lymphatic Leukemia ◽  
Rare Association ◽  
Lymphatic Leukemia ◽  
History Of

A 30-year-old housewife with past history of acute lymphoblastic leukemia 12 years back, still in remission, was admitted with polyarthritis of 2 months duration. She was evaluated and found to have SLE with positive ANA and Anti ds DNA which were strongly positive.

Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk non-T, non-B acute lymphocytic leukemia: A Pediatric Oncology Group study.

1994 ◽  
Vol 12 (7) ◽  
pp. 1383-1389 ◽  
Author(s):  
B Camitta ◽  
D Mahoney ◽  
B Leventhal ◽  
S J Lauer ◽  
J J Shuster ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Lymphocytic Leukemia ◽  
Remission Induction ◽  
Intrathecal Therapy ◽  
Free Survival ◽  
Continuation Therapy ◽  
Potential Efficacy ◽  
Patients At Risk ◽  
B Lineage

PURPOSE To determine the potential efficacy and toxicity of intravenous (i.v.) methotrexate (MTX) and mercaptopurine (MP) as postremission intensification treatment for children with B-lineage acute lymphoblastic leukemia (ALL) at higher risk to relapse. PATIENTS AND METHODS Eighty-three patients (age 1 to 20 years) with higher-risk B-lineage ALL were entered onto this protocol. Following standard four-drug remission induction, 80 patients received 12 intensive 2-week cycles of MTX/MP: MTX 200 mg/m2 i.v. push, then 800 mg/m2 i.v. 24-hour infusion on day 1; MP 200 mg/m2 i.v. in 20 minutes, then 800 mg/m2 i.v. 8-hour infusion day 2; MTX 20 mg/m2 intramuscularly day 8; and MP 50 mg/m2 by mouth days 8 to 14. Age-based triple intrathecal therapy (MTX, hydrocortisone, and cytarabine) was administered for CNS prophylaxis. Continuation therapy was weekly MTX/MP (as on days 8 to 14) for 2 years. RESULTS Eighty-one patients (98%) entered remission. There were 28 relapses (marrow, n = 11; marrow and CNS, n = 2; isolated CNS, n = 9; testes, n = 5; ovaries, n = 1). No overt relapse occurred during the intensive phase of therapy. The event-free survival (EFS) rate at 4 years is 57.4% +/- 9.1% (SE). Hematologic, mucosal, and infectious toxicities were seen in 12%, 9%, and 5% of intensive MTX/MP courses, but were generally mild. CONCLUSION Combined data from this and our previous trial suggest that intensive MTX/MP may produce long-term disease-free survival in 70 to 75% of children with B-lineage ALL. In comparison to other intensive regimens, intensive MTX/MP is easy to administer, effective, and relatively nontoxic. If patients at risk for failure of MTX/MP can be identified prospectively, more aggressive regimens could be restricted to this smaller (25% to 30%) cohort.

scholarly journals Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Retrospective Multinational Study

2019 ◽  
Vol 37 (10) ◽  
pp. 770-779 ◽  
Author(s):  
Ching-Hon Pui ◽  
Paola Rebora ◽  
Martin Schrappe ◽  
Andishe Attarbaschi ◽  
Andre Baruchel ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Survival Rate ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Remission Induction ◽  
Event Free Survival ◽  
Free Survival

PURPOSE We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials. PATIENTS AND METHODS This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome. RESULTS With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction. CONCLUSION MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.

A New Genotyping Chip for Childhood ALL: Using a Novel Multiplex Allele-Specific Primer Extension Strategy To Detect Twelve Polymorphisms in Six Genes Encoding for Drug-Metabolizing Enzymes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4500-4500
Author(s):  
Yi Lu ◽  
Kow-Yin Kham ◽  
Eng-Juh Yeoh
Keyword(s):  
Drug Metabolism ◽  
Imaging System ◽  
Lymphoblastic Leukemia ◽  
Asian Population ◽  
Genome Project ◽  
Dna Chip ◽  
Specific Primer ◽  
Childhood All ◽  
Polymorphic Genes ◽  
Allele Specific

Abstract Background/Aim Despite great improvements in the treatment of childhood Acute Lymphoblastic Leukemia (ALL), resistant to treatment still remains a leading cause of cancer-related death in children. Although the underlying mechanism is not well understood, studies have shown that polymorphisms in those genes involved in drug metabolism may not only modify the susceptibility to the cancer but also influence the risk of relapse. Knowledge of patient’s pharmacogenetic make-up thus becomes important as we will move into a new era of individualizing therapy within the next decade. With the completion of the Human Genome Project, there is huge information on the SNPs which are involved in the drug metabolism. Hence, a highly efficient genotyping strategy is required to study multiple candidate genes on a single platform. This will provide timely reports for oncologists to tailor treatments for patients based on their pharmacogenetic constitution. Therefore, we aimed to develop an integrative genotyping platform, a DNA chip capable of detecting several mutations simultaneously. We plan to use this new tool to investigate the roles of 12 polymorphisms in 6 important drug-metabolizing genes (Table 1) in the risk of ALL as well as their impact on the treatment outcome in our Southeast Asian population, where only a few pharmacogenetic studies have been reported. Methods Two allele-specific primers are designed to interrogate each polymorphism and all primers for wild-type or mutant are pooled to obtain 2 mixtures. Eleven fragments spanning 12 polymorphic alleles are amplified in 3 multiplex PCR and pooled, followed by multiplex allele-specific primer extensions using 2 primer mixtures respectively. Only fully matched primers will be extended with TAMRA-labelled ddNTP. The products are subsequently loaded on DNA chip and the extended primers are captured by corresponding complementary oligo tags. The fluorescence will then disclose the genotype in imaging system. Currently we have used 40 DNA control samples to validate this platform. Results Homozygosity displayed fluorescence from only 1 allele while signals from both indicated heterozygosity (Fig 1). We have performed PCR-RFLP tests on NQO1, MTHFR and GSTP1, and used those results to verify the accuracy of the chip. 96.7% accuracy has been achieved. Conclusion Our preliminary results have demonstrated the validity of this novel genotyping strategy which has great potential to become a simple and reliable method for pharmacogenetics study. Future Plan Further verification and optimization are in progress. We will finally apply this genotyping strategy to screen childhood ALL patient samples to study the influence of these polymorphic genes on the disease. The 6 polymorphic genes involved in drug metabolism Figure Figure Gene Polymorphism(s) Drugs affected TPMT *3A (G460A, A719G), *6 (A539T) 6-mercaptopurine, 6-thioguanine NQO1 *2 (C609T) Alkylators CYP1A1 *2A (T6235C), *2B (A4889G, T6235C), *4 (C4887A) others CYP2D6 *3 (A2637 deletion), *4 (G1934A) others GSTP1 A105G Glucocorticoids MTHFR C677T, A1298C Methotrexate

A Multicenter Phase II Study Using a Dose Intensified Pediatric Regimen in Adults with Untreated Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1858-1858 ◽  
Author(s):  
Daniel J. DeAngelo ◽  
Lewis B. Silverman ◽  
Stephen Couban ◽  
Suzanne Dahlberg ◽  
Philip C. Amrein ◽  
...  
Keyword(s):  
Phase Ii ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Demographic Data ◽  
Philadelphia Chromosome ◽  
Remission Induction ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Childhood All

Abstract Background: In children with ALL, current chemotherapy regimens produce an event-free survival (EFS) of greater than 80%. Adults with ALL have a much poorer prognosis, with EFS rates of 30–40%. Recent retrospective studies suggest that young adult patients may have superior outcomes when treated on more intensive pediatric regimens, but prospective studies are lacking. A phase II trial was performed in an effort to determine if an intensive pediatric regimen can be administered to adults with ALL. Methods: The therapeutic backbone of this protocol is based upon the high-risk arm of the DFCI Childhood ALL Consortium Protocol 00–01. Patients with newly diagnosed ALL were enrolled and received intensive multiagent remission induction chemotherapy, which included doxorubicin, prednisone, vincristine, high-dose methotrexate, high-dose asparaginase, and triple intrathecal therapy. CNS prophylaxis included triple intrathecal therapy and cranial radiation. Intensification therapy consisted of 3 week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine and 30 weeks of high-dose asparaginase that was individually dosed in order to maintain asparagine depletion. Continuation therapy consisted of 3 week courses of vincristine, dexamethasone, methotrexate and 6-mercaptopurine for a total of 2 years from an established complete remission (CR). Results: 71 patients have been enrolled to date. Although there was no initial upper age restriction, the protocol was amended to include only patients between the ages of 18–50 with de novo ALL; this amendment excluded 4 patients from the analysis. Two patients were enrolled but never received therapy. Demographic data are available for 61 evaluable patients. The median age was 28 years, (range, 18–50), 65% were male, 75% had B-lineage phenotype, and 13% were Philadelphia chromosome positive. In the 54 patients for whom response data was available, the 4 week CR rate was 82%. Among the patients who had the opportunity to complete Intensification therapy, asparaginase data was available for 23 patients, 18 (78%) of whom completed all 30 weeks. One death occurred during induction therapy from sepsis. Four patients developed grade 3 pancreatitis and one patient died of grade 5 pancreatitis. The latter case represented the only remission death on study. There were two cases of osteonecrosis, 10 cases of thrombosis/embolism and 12 cases of neutropenic infection that occurred during the post-remission period. At the median follow-up time of 18.4 months, the estimated EFS is 75% (95%CI: 61–89%) and the overall survival is 79% (95%CI: 65–93%). Conclusions: These results suggest that administration of a dose intensified pediatric-like strategy is feasible. Although the high EFS rate requires longer follow up and larger confirmatory studies, such intensive treatment of young adults with ALL could represent a major therapeutic advance.

Line Treatment of Adult Ph+ Acute Lymphoblastic Leukemia (ALL) Patients. Final Results of the GIMEMA LAL1205 Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 305-305 ◽  
Author(s):  
Robert Foà ◽  
Antonella Vitale ◽  
Anna Guarini ◽  
Maria Sefania De Propris ◽  
Loredana Elia ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Leukemic Cells ◽  
Remission Induction ◽  
Induction Treatment ◽  
Induction Phase ◽  
Significant Prognostic Factor ◽  
Rt Pcr ◽  
Active Inhibitor

Abstract Background: Dasatinib is a potent, oral inhibitor of the BCR-ABL, c-KIT and SRC kinase family, which has proven to be a more active inhibitor of BCR-ABL and c-KIT than imatinib in preclinical studies. Clinically, it has been shown to be effective in chronic myeloid leukemia and in Ph+ ALL patients resistant or intolerant to imatinib. Aims: The primary objective of the study was to assess the activity of dasatinib in de novo adult Ph+ ALL patients in terms of complete hematological remission (CHR); the secondary objectives were treatment toxicity, rate of immunophenotypic and molecular responses, disease-free survival (DFS), relapse rate and overall survival (OS). Methods: The GIMEMA LAL 1205 protocol was designed for patients ≥18 years (no upper age limit) who receive dasatinib po, 70 mg BID. A steroid pre-phase is started 7 days prior to dasatinib administration and continued up to day 31, and then tapered. The pre-phase allows identification of the BCR/ABL transcript. Dasatinib is given for 12 weeks. Two intrathecal methotrexates are administered at days +22 and +43. All cases are analyzed through a central handling of samples at presentation for morphology, immunophenotype, cytogenetics and molecular biology at the coordinating center in Rome. Minimal residual disease (MRD) is also centrally investigated by flow-cytometry and Q-RT-PCR at days +22, +43, +57 and +84. The protocol was designed for 48 patients. Results: Recruitment started in November 2006 and was completed in August 2008. The median age of the 48 enrolled BCR/ABL+ ALL patients was 54 years (range 24-76), 26 were females and 22 males. The median WBC count was 20.1 (range 2.2–133). The last analysis has been conducted on 36 patients. One patient stopped treatment after 14 days due to intestinal toxicity and 1 patient refused treatment. Thus, to date 34 patients are evaluable for response. Nineteen cases were p190+ and 15 p210+ (5 were p190/p210+). A &gt;75% response to the steroid pre-phase was recorded in 82.7% of patients. All 34 patients (100%) have witnessed a CHR: 32 (94.12%) at the 1st determination at day +22, 1 at the 2nd at day +43 and 1 at the 3rd at day +57. No fatalities have been observed. In 13 patients, at least 1 severe adverse event (SAE) has been recorded, for a total of 26 SAEs. Overall, the compliance has been good; only 1 patient stopped treatment at day 67 due to toxicity while in CHR. The median follow-up is so far 11.2 months. The OS at 10 months is 80.7%. Immunophenotypic and BCR/ABL Q-RT-PCR monitoring of MRD has shown a very marked clearance of leukemic cells by day +22, progressively strengthened at the subsequent timepoints. In p190+ cases the minimal MRD value was reached at day +43, while in p210+ cases this was observed at day +84, documenting a lower susceptibility to dasatinib by this molecular subgroup. So far, 9 patients have relapsed, at a median of 72 days from the end of induction; in agreement with the MRD data, 7/9 relapses occurred within the p210+ cases and 2/9 within the p190+ cases. The presence of mutations has been investigated in 8/9 relapsed samples: 5 showed a T315I mutation, 1 an E255K mutation and 2 were wt. Cloning experiments allowed to detect in 2 cases low levels of T315I mutations already at presentation and on MRD cells at the end of the induction treatment. The first multivariate analysis has been conducted for DFS and the degree of PCR reduction − ≤10−3 vs ≥10−3 - has so far emerged as the only significant prognostic factor. Conclusions: This study demonstrates that in adult Ph+ ALL dasatinib monotherapy is capable of inducing a CHR in virtually all patients, irrespective of age, without important toxicities and with no fatalities. The hematological response is associated with a very marked and rapid debulking of the neoplastic clone documented at the MRD level, particularly for p190+ cases. The degree of PCR response is of prognostic relevance. No relapses have been observed during the induction phase. The optimal post-induction treatment strategy, which was not part of the study, remains to be defined, particularly in light of the genetic instability of Ph+ ALL and of the selection/induction of mutations. These results, together with those previously reported by our group with imatinib alone for elderly patients, question the use of chemotherapy, with or without a TK inhibitor, for the remission induction of Ph+ ALL.

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