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ABSTRACT: Children with acute lymphocytic leukemia who fail to enter remission have a poor prognosis. In a previous study, 9 of 14 children with induction failure entered remission after teniposide (VM26) plus cytosine arabinoside (Ara-C). We attempted to confirm these results. Twenty children received teniposide (200 mg/m/day IV) for 3 days and cytosine arabinoside (100 mg/m/day continuous IV infusion) for 7 days. There were 3 complete and 3 partial responses. Two additional patients achieved a complete response after a second, shorter course of the same agents. Although VM26 plus Ara-C is an active combination for treatment of acute lymphocytic leukemia induction failure, it does not appear as effective as in the initial report. Better treatments for this problem are needed.
Journal of Pediatric Hematology/Oncology 11/2012; · 1.16 Impact Factor
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Denise M Oliansky, Bruce Camitta,
Paul Gaynon,
Michael L Nieder,
Susan K Parsons,
Michael A Pulsipher,
Hildy Dillon,
Thomas A Ratko,
Donna Wall,
Philip L McCarthy,
Theresa Hahn
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2012; 18(7):979-81. · 3.15 Impact Factor
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ABSTRACT: Infants (<366 days of age) with acute lymphoblastic leukemia (ALL) have a poor prognosis. Most treatment failures occur within 6-9 months of diagnosis, primarily from relapse.
The Children's Oncology Group P9407 study was designed to test if early intensified treatment would improve outcome for infants with ALL. Due to a significant number of early deaths (< 90 days from enrollment), Induction therapy was amended three times. Cohorts 1 + 2 (n = 68), received identical Induction therapy except for reduced daunorubicin dose in Cohort 2. Cohort 3 (n = 141) received prednisone (40 mg/m(2) /day) instead of dexamethasone (10 mg/m(2) /day) and short infusion daunorubicin (30 minutes) instead of continuous infusion (48 hours), as well as additional supportive care measures throughout therapy.
Early deaths occurred in 17/68 (25%) infants in Cohorts 1 + 2 and 8/141 (5.7%) infants in Cohort 3 (P < 0.0001). Among infants ≤90 days of age at diagnosis, early death occurred in 10/17 (58.8%) in Cohorts 1 + 2 and 4/27 (14.8%) in Cohort 3 (P = 0.006). Among infants >90 days of age at diagnosis, early death occurred in 7/51 (13.7%) in Cohorts 1 + 2 and 4/114 (3.5%) in Cohort 3 (P = 0.036). Bacterial, viral, and fungal infections were more common in Cohorts 1 + 2 versus Cohort 3.
Early morbidity and mortality for infants with ALL were reduced by substitution of prednisone (40 mg/m(2) /day) for dexamethasone (10 mg/m(2) /day), the delivery of daunorubicin over 30 minutes instead of a continuous infusion for 48 hours, and the provision of more specific supportive care measures. Pediatr Blood Cancer 2012; 59: 834-839. © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer 04/2012; 59(5):834-9. · 1.89 Impact Factor
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Huining Kang,
Carla S Wilson,
Richard C Harvey,
I-Ming Chen,
Maurice H Murphy,
Susan R Atlas,
Edward J Bedrick,
Meenakshi Devidas,
Andrew J Carroll,
Blaine W Robinson, [......],
Nyla A Heerema,
Joanne M Hilden,
Carolyn A Felix,
Gregory H Reaman, Bruce Camitta,
Naomi Winick,
William L Carroll,
ZoAnn E Dreyer,
Stephen P Hunger,
Cheryl L Willman
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ABSTRACT: Gene expression profiling was performed on 97 cases of infant ALL from Children's Oncology Group Trial P9407. Statistical modeling of an outcome predictor revealed 3 genes highly predictive of event-free survival (EFS), beyond age and MLL status: FLT3, IRX2, and TACC2. Low FLT3 expression was found in a group of infants with excellent outcome (n = 11; 5-year EFS of 100%), whereas differential expression of IRX2 and TACC2 partitioned the remaining infants into 2 groups with significantly different survivals (5-year EFS of 16% vs 64%; P < .001). When infants with MLL-AFF1 were analyzed separately, a 7-gene classifier was developed that split them into 2 distinct groups with significantly different outcomes (5-year EFS of 20% vs 65%; P < .001). In this classifier, elevated expression of NEGR1 was associated with better EFS, whereas IRX2, EPS8, and TPD52 expression were correlated with worse outcome. This classifier also predicted EFS in an independent infant ALL cohort from the Interfant-99 trial. When evaluating expression profiles as a continuous variable relative to patient age, we further identified striking differences in profiles in infants less than or equal to 90 days of age and those more than 90 days of age. These age-related patterns suggest different mechanisms of leukemogenesis and may underlie the differential outcomes historically seen in these age groups.
Blood 12/2011; 119(8):1872-81. · 9.90 Impact Factor
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Denise M Oliansky, Bruce Camitta,
Paul Gaynon,
Michael L Nieder,
Susan K Parsons,
Michael A Pulsipher,
Hildy Dillon,
Thomas A Ratko,
Donna Wall,
Philip L McCarthy,
Theresa Hahn
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ABSTRACT: Clinical research published since the first evidence-based review on the role of hematopoietic stem cell transplantation (SCT) in the treatment of pediatric acute lymphoblastic leukemia (ALL) is presented and critically evaluated in this update. Treatment recommendations are provided by an expert panel. Allogeneic SCT is recommended for children who: are in second complete remission (CR2) after experiencing an early marrow relapse for precursor-B ALL; experienced primary induction failure, but subsequently achieved a CR1; have T-lineage ALL in CR2; or have ALL in third or greater remission. Although the 2005 pediatric ALL evidence-based review (EBR) recommended allogeneic SCT for children with Philadelphia chromosome positive (Ph+) ALL in CR1, preliminary tyrosine kinase inhibitor (TKI) data demonstrate that early outcomes are comparable for allogeneic SCT and chemotherapy + imatinib. Based on the evidence, autologous SCT is not recommended for ALL in CR1. Allogeneic SCT is not recommended for: T-lineage ALL in CR1; mixed-lineage leukemia (MLL)+ ALL when it is the sole adverse risk factor; isolated central nervous system (CNS) relapse in precursor-B ALL. Based on expert opinion, allogeneic SCT may be considered for hypodiploid ALL and persistent matched related donor (MRD) positivity in ALL in CR1 or greater, although these are areas that need further study. Treatment recommendations pertaining to various transplantation techniques are also provided, as are areas of needed future research.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2011; 18(4):505-22. · 3.15 Impact Factor
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ZoAnn E Dreyer,
Patricia A Dinndorf, Bruce Camitta,
Harland Sather,
Mei K La,
Meenakshi Devidas,
Joanne M Hilden,
Nyla A Heerema,
Jean E Sanders,
Ron McGlennen,
Cheryl L Willman,
Andrew J Carroll,
Fred Behm,
Franklin O Smith,
William G Woods,
Kamar Godder,
Gregory H Reaman
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ABSTRACT: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with current therapy, the event-free survival (EFS) of infants with ALL, particularly those with mixed lineage leukemia (MLL) gene rearrangements, is only 30% to 40%. Relapse has been the major source of treatment failure for these patients. The parallel Children's Cancer Group (CCG) 1953 and Pediatric Oncology Group (POG) 9407 studies were designed to test the hypothesis that more intensive therapy, including dose intensification of chemotherapy, and hematopoietic stem-cell transplantation (HSCT) would improve the outcome for this group of patients.
One hundred eighty-nine infants (CCG 1953, n = 115; POG 9407, n = 74) were enrolled between October 1996 and August 2000. For infants with the MLL gene rearrangement and an appropriate donor, HSCT was the preferred treatment on CCG 1953 and investigator option on POG 9407 after completion of the second phase of therapy. Fifty-three infants underwent HSCT.
The 5-year EFS rate was 48.8% (95% CI, 33.9% to 63.7%) in patients who received HSCT and 48.7% (95% CI, 33.8% to 63.6%) in patients treated with chemotherapy alone (P = .60). Transplantation outcomes were not affected by the preparatory regimen or donor source.
Our data suggest that routine use of HSCT for infants with MLL-rearranged ALL is not indicated. However, limited by small numbers, this study should not be considered the definitive answer to this question.
Journal of Clinical Oncology 01/2011; 29(2):214-22. · 18.37 Impact Factor
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Richard C Harvey,
Charles G Mullighan,
Xuefei Wang,
Kevin K Dobbin,
George S Davidson,
Edward J Bedrick,
I-Ming Chen,
Susan R Atlas,
Huining Kang,
Kerem Ar, [......],
James R Downing,
Mary Relling,
Jun Yang,
Deepa Bhojwani,
William L Carroll, Bruce Camitta,
Gregory H Reaman,
Malcolm Smith,
Stephen P Hunger,
Cheryl L Willman
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ABSTRACT: To resolve the genetic heterogeneity within pediatric high-risk B-precursor acute lymphoblastic leukemia (ALL), a clinically defined poor-risk group with few known recurring cytogenetic abnormalities, we performed gene expression profiling in a cohort of 207 uniformly treated children with high-risk ALL. Expression profiles were correlated with genome-wide DNA copy number abnormalities and clinical and outcome features. Unsupervised clustering of gene expression profiling data revealed 8 unique cluster groups within these high-risk ALL patients, 2 of which were associated with known chromosomal translocations (t(1;19)(TCF3-PBX1) or MLL), and 6 of which lacked any previously known cytogenetic lesion. One unique cluster was characterized by high expression of distinct outlier genes AGAP1, CCNJ, CHST2/7, CLEC12A/B, and PTPRM; ERG DNA deletions; and 4-year relapse-free survival of 94.7% ± 5.1%, compared with 63.5% ± 3.7% for the cohort (P = .01). A second cluster, characterized by high expression of BMPR1B, CRLF2, GPR110, and MUC4; frequent deletion of EBF1, IKZF1, RAG1-2, and IL3RA-CSF2RA; JAK mutations and CRLF2 rearrangements (P < .0001); and Hispanic ethnicity (P < .001) had a very poor 4-year relapse-free survival (21.0% ± 9.5%; P < .001). These studies reveal striking clinical and genetic heterogeneity in high-risk ALL and point to novel genes that may serve as new targets for diagnosis, risk classification, and therapy.
Blood 12/2010; 116(23):4874-84. · 9.90 Impact Factor
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ABSTRACT: Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in children and adolescents has, until recently, been considered one of the poorest-risk subgroups of ALL. With chemotherapy alone, only 20-30% of children with Ph(+) ALL are cured. Allogeneic hematopoietic cell transplantation in first complete remission cures 60% of patients with a closely matched donor. Although targeted tyrosine kinase inhibitors (TKIs) have limited activity against Ph(+) ALL as a single agent, they have been evaluated in combination with chemotherapy with promising results. The early results of Children's Oncology Group trial AALL0031 have shown 88% 3-year event-free survival for Ph(+) patients treated with intensive chemotherapy plus continuous-dosing imatinib. This suggests that chemotherapy plus TKIs may be the initial treatment of choice for Ph(+) ALL in children. However, the numbers are small in this trial and confirmatory results are not yet available from the European Intergroup Study on Post Induction Treatment of Philadelphia Positive Acute Lymphoblastic Leukaemia with Imatinib trial. Additional issues include determining the most effective TKI (imatinib, dasatinib or nilotinib) and the most effective, least toxic chemotherapy backbone. The experience of adding a targeted agent such as a TKI to the standard chemotherapy regimen suggests that this strategy might be applied to other ALL subtypes to achieve both increased efficacy and decreased toxicity.
Expert Review of Hematology 12/2010; 3(6):731-42. · 1.16 Impact Factor
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Roland Chu,
Ruta Brazauskas,
Fangyu Kan,
Asad Bashey,
Christopher Bredeson, Bruce Camitta,
Kuang-Yueh Chiang,
Haydar Frangoul,
Robert Peter Gale,
Adrian Gee, [......],
Vikas Gupta,
Gregory A Hale,
Luis Isola,
Alvaro Urbano Ispizua,
Hillard Lazarus,
Judith Marsh,
James Russell,
Mitchell Sabloff,
Edmund K Waller,
Mary Eapen
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ABSTRACT: We compared outcomes of patients with severe aplastic anemia (SAA) who received granulocyte-colony stimulating factor (G-CSF)-stimulated bone marrow (G-BM) (n = 78), unstimulated bone marrow (BM) (n = 547), or peripheral blood progenitor cells (PBPC) (n = 134) from an HLA-matched sibling. Transplantations occurred in 1997 to 2003. Rates of neutrophil and platelet recovery were not different among the 3 treatment groups. Grade 2-4 acute graft-versus-host disease (aGVHD) (relative risk [RR] = 0.82, P = .539), grade 3-4 aGVHD (RR = 0.74, P = .535), and chronic GVHD (cGVHD) (RR = 1.56, P = .229) were similar after G-BM and BM transplants. Grade 2-4 aGVHD (RR = 2.37, P = .012) but not grade 3-4 aGVHD (RR = 1.66, P = .323) and cGVHD (RR = 5.09, P < .001) were higher after PBPC transplants compared to G-BM. Grade 2-4 (RR = 2.90, P < .001), grade 3-4 (RR = 2.24, P = .009) aGVHD and cGVHD (RR = 3.26, P < .001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR = 0.63, P = .05). These data suggest no advantage to using G-BM and the observed higher rates of aGVHD and cGVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA-matched sibling transplants for SAA.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2010; 17(7):1018-24. · 3.15 Impact Factor
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Judith Marsh,
Gerard Socie,
Andre Tichelli,
Hubert Schrezenmeier,
Britta Hochsmann,
Antonio M Risitano,
Monika Fuehrer,
Albert N Bekassy,
Elizabeth T Korthof,
Anna Locasciulli,
Per Ljungman,
Andrea Bacigalupo, Bruce Camitta,
Neal S Young,
Jakob Passweg
British Journal of Haematology 08/2010; 150(3):377-9. · 4.94 Impact Factor
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Kirk R Schultz,
W Paul Bowman,
Alexander Aledo,
William B Slayton,
Harland Sather,
Meenakshi Devidas,
Chenguang Wang,
Stella M Davies,
Paul S Gaynon,
Michael Trigg,
Robert Rutledge,
Laura Burden,
Dean Jorstad,
Andrew Carroll,
Nyla A Heerema,
Naomi Winick,
Michael J Borowitz,
Stephen P Hunger,
William L Carroll, Bruce Camitta
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ABSTRACT: Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups.
We evaluated whether imatinib (340 mg/m(2)/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph- ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) -identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT.
Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% +/- 11% (95% CI, 64% to 90%), more than twice historical controls (35% +/- 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% +/- 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% +/- 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction.
Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.
Journal of Clinical Oncology 10/2009; 27(31):5175-81. · 18.37 Impact Factor
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Jeffrey E Rubnitz,
David Wichlan,
Meenakshi Devidas,
Jonathan Shuster,
Stephen B Linda,
Joanne Kurtzberg,
Beverly Bell,
Stephen P Hunger,
Allen Chauvenet,
Ching-Hon Pui, Bruce Camitta,
Jeanette Pullen
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ABSTRACT: To prospectively determine the prognostic significance of the TEL-AML1 fusion in children with acute lymphoblastic leukemia (ALL).
TEL gene status was determined for 926 patients with B-precursor ALL enrolled on the Pediatric Oncology Group ALinC 16 trials and patients were observed for a median time of 8 years.
Rearrangements of the TEL gene were detected in 244 patients (26%). The estimated 5-year event-free survival rate (+/- SE) for patients with TEL rearrangements was 86% +/- 2%, compared with 72% +/- 2% for those with germline TEL (P < .0001). TEL rearrangements were associated with a superior outcome among patients with standard-risk ALL, high-risk ALL, and rapid early responses to therapy. In a multivariate analysis that included risk group, sex, and day 15 marrow status, TEL status was an independent predictor of outcome (P = .0002).
We conclude that TEL gene status should be incorporated into risk classification schemes and suggest that patients who have standard-risk features, the TEL-AML1 fusion, and rapid early responses to therapy, should be treated with antimetabolite-based therapy designed to maintain their high cure rates and avoid late effects.
Journal of Clinical Oncology 06/2008; 26(13):2186-91. · 18.37 Impact Factor
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ABSTRACT: At concentrations >0.1 mM, hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU (1200 mg/m2) was followed 2 hours later by ara-C (250-3100 mg/m2) intravenously in 15 minutes. The combination was given on days 1, 2, 3 and 8, 9, 10. Thirty-three children [26 acute lymphocytic leukemia (ALL), 7 acute nonlymphocytic leukemia] were treated; 29 received at least 1 full course. All patients developed grade 4 cytopenias. Other grade 3 to 4 toxicities included hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9), and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5 ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1 to 3 mo). Twenty of twenty-six patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range: 0.21 to 0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism.
Journal of Pediatric Hematology/Oncology 05/2008; 30(5):353-7. · 1.16 Impact Factor
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James B Nachman,
Nyla A Heerema,
Harland Sather, Bruce Camitta,
Erik Forestier,
Christine J Harrison,
Nicole Dastugue,
Martin Schrappe,
Ching-Hon Pui,
Giuseppe Basso,
Lewis B Silverman,
Gritta E Janka-Schaub
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ABSTRACT: One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploidy (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% +/- 4.4% and 49.8% +/- 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P = .01; 8-year estimate, 52.2% vs 30.1%) and OS (P = .017; 69% vs 37.5%). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse EFS but similar OS. Doubling of the hypodiploid clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33-39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy.
Blood 09/2007; 110(4):1112-5. · 9.90 Impact Factor
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Allen R Chauvenet,
Paul L Martin,
Meenakshi Devidas,
Stephen B Linda,
Beverly A Bell,
Joanne Kurtzberg,
Jeanette Pullen,
Mark J Pettenati,
Andrew J Carroll,
Jonathan J Shuster, Bruce Camitta
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ABSTRACT: Pediatric Oncology Group (POG) protocol 9201 enrolled children with lesser-risk B-lineage acute lymphoblastic leukemia (ALL) defined by age (1-9), white blood cell count (WBC) less than 50 x 10(9)/L (50,000/microL), DNA findings of trisomies 4 and 10 (or DNA index > 1.16), and lack of overt central nervous system (CNS) leukemia. After vincristine, prednisone, and asparaginase induction, 650 of 653 eligible patients attained remission (3 induction deaths) and received 6 courses of intravenous methotrexate (1 g/m(2)) with daily mercaptopurine. Weekly intramuscular methotrexate was added during maintenance; pulses of vincristine and prednisone were administered with periodic intrathecal chemotherapy. Treatment duration was 2.5 years. No alkylators, epipodophylotoxins, anthracyclines, or radiation were given. The 6-year event-free survival (EFS) was 86.6% with overall survival (OS) of 97.2%. Patients with less than 5% marrow blasts on induction day 15 had superior EFS. A difference not reaching conventional statistical significance (P = .068) was noted for superior outcomes in patients with trisomies of chromosomes 4 and 10 versus those lacking double trisomies. Sex, ethnicity, CNS status, and WBC were not predictive. This indicates the great majority of children with lesser-risk B-lineage ALL are curable without agents with substantial late effects.
Blood 09/2007; 110(4):1105-11. · 9.90 Impact Factor
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ABSTRACT: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration.
Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window.
Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% +/- 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% +/- 11.3% and 77.7% +/- 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% +/- 10.8% and 80.2% +/- 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported.
Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.
Journal of Clinical Oncology 08/2006; 24(19):3142-9. · 18.37 Impact Factor
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Mary Eapen,
Elizabeth Raetz,
Mei-Jie Zhang,
Catherine Muehlenbein,
Meenakshi Devidas,
Thomas Abshire,
Amy Billett,
Alan Homans, Bruce Camitta,
William L Carroll,
Stella M Davies
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ABSTRACT: The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (< 36 months), risk of a second relapse was significantly lower after total body irradiation (TBI)-containing transplant regimens (relative risk [RR], 0.49; 95% confidence interval [CI] 0.33-0.71, P < .001) than chemotherapy regimens. In contrast, for children with a late first relapse (> or = 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.
Blood 07/2006; 107(12):4961-7. · 9.90 Impact Factor
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Theresa Hahn,
Donna Wall, Bruce Camitta,
Stella Davies,
Hildy Dillon,
Paul Gaynon,
Richard A Larson,
Susan Parsons,
Jerome Seidenfeld,
Daniel Weisdorf,
Philip L McCarthy
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ABSTRACT: Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute lymphoblastic leukemia in adults (> or =15 years) is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published medical literature and for grading the quality and strength of the evidence, and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented and were reached unanimously by a panel of acute lymphoblastic leukemia experts. The priority areas of needed future research for adult acute lymphoblastic leukemia are: definition of patients at high risk in first complete remission, beyond Philadelphia chromosome positive; outcomes of SCT in older (>50 years) adults; determination if reduced intensity versus myeloablative conditioning regimens yield an equivalent graft-versus-leukemia effect with reduced toxicity; monitoring of minimal residual disease to achieve disease control before SCT; and the use of cord blood and other alternative sources of stem cells for use in adult SCT recipients.
Biology of Blood and Marrow Transplantation 01/2006; 12(1):1-30. · 3.87 Impact Factor
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Journal of Pediatric Hematology/Oncology 01/2006; 27(12):696-8. · 1.16 Impact Factor
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Theresa Hahn,
Donna Wall, Bruce Camitta,
Stella Davies,
Hildy Dillon,
Paul Gaynon,
Richard A Larson,
Susan Parsons,
Jerome Seidenfeld,
Daniel Weisdorf,
Philip L McCarthy
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ABSTRACT: Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute lymphoblastic leukemia (ALL) in children is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in a table in this review (Summary of Treatment Recommendations Made by the Expert Panel for Pediatric Acute Lymphoblastic Leukemia) and were reached unanimously by a panel of ALL experts. The priority areas of needed future research in pediatric ALL are unrelated marrow or blood donor versus unrelated cord blood donor allogeneic SCT; alternative, nonfamily allogeneic donor versus autologous SCT; better methods for identifying high-relapse-risk patients; assessments of the effect of current chemotherapy regimens on early relapse; and use of pre-SCT detection of minimal residual disease to predict post-SCT outcomes.
Biology of Blood and Marrow Transplantation 12/2005; 11(11):823-61. · 3.87 Impact Factor
