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ABSTRACT: X-linked lymphoproliferative syndrome (XLP) is caused by mutations in SH2D1A, and is associated with overwhelming infectious mononucleosis, aplastic anemia, hypogammaglobulinemia, and B-cell lymphomas. However, the frequency of SH2D1A mutations in males who present with B NHL is unknown. Five cases of XLP were diagnosed among 158 males presenting with B NHL (approximately 3.2%). Four of the patients had two episodes of B NHL and one had a single episode of B NHL followed by aggressive infectious mononucleosis. Prospective screening for XLP in males with B-cell lymphoma at the time of initial diagnosis should be considered. Pediatr Blood Cancer. © 2013 Wiley Periodicals, Inc.
Pediatric Blood & Cancer 04/2013; · 1.89 Impact Factor
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D Bhojwani,
D Pei,
J T Sandlund,
S Jeha,
R C Ribeiro,
J E Rubnitz,
S C Raimondi,
S Shurtleff, M Onciu,
C Cheng,
E Coustan-Smith,
W P Bowman,
S C Howard,
M L Metzger,
H Inaba,
W Leung,
W E Evans,
D Campana,
M V Relling,
C-H Pui
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ABSTRACT: ETV6-RUNX1 fusion is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL). To evaluate whether outcomes for this drug-sensitive leukemia are improved by contemporary risk-directed therapy, we studied clinical features, response and adverse events of 168 children with newly diagnosed ETV6-RUNX1-positive ALL on St Jude Total Therapy studies XIIIA (N=36), XIIIB (N=38) and XV (N=94). Results were compared with 494 ETV6-RUNX1-negative B-precursor ALL patients. ETV6-RUNX1 was associated with age 1-9 years, pre-treatment classification as low risk and lower levels of minimal residual disease (MRD) on day 19 of therapy (P<0.001). Event-free survival (EFS) or overall survival (OS) did not differ between patients with or without ETV6-RUNX1 in Total XIIIA or XIIIB. By contrast, in Total XV, patients with ETV6-RUNX1 had significantly better EFS (P=0.04; 5-year estimate, 96.8±2.4% versus 88.3±2.5%) and OS (P=0.04; 98.9±1.4% versus 93.7±1.8%) than those without ETV6-RUNX1. Within the ETV6-RUNX1 group, the only significant prognostic factor associated with higher OS was the treatment protocol Total XV (versus XIIIA or XIIIB) (P=0.01). Thus, the MRD-guided treatment schema including intensive asparaginase and high-dose methotrexate in the Total XV study produced significantly better outcomes than previous regimens and demonstrated that nearly all children with ETV6-RUNX1 ALL can be cured.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2011; 26(2):265-70. · 8.30 Impact Factor
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J T Sandlund,
C-H Pui,
H Mahmoud,
Y Zhou,
E Lowe,
S Kaste,
L E Kun,
M J Krasin, M Onciu,
F G Behm,
R C Ribeiro,
B I Razzouk,
S C Howard,
M L Metzger,
G A Hale,
R Rencher,
K Graham,
M M Hudson
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ABSTRACT: Children with recurrent or refractory malignant lymphoma generally have a poor prognosis. There is a need for new active drug combinations for this high-risk group of patients.
This study evaluated the activity and toxicity of the methotrexate, ifosfamide, etoposide and dexamethasone (MIED) regimen for childhood refractory/recurrent non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma (HL). From 1991 through 2006, 62 children with refractory/recurrent NHL (n = 24) or HL (n = 38) received one to six cycles of MIED. Based on MIED response, intensification with hematopoietic stem cell transplantation (HSCT) was considered.
There were 10 complete (CR) and 5 partial responses (PR) among the 24 children with NHL [combined response rate, 63%; 95% confidence interval (CI) 38% to 73%]. There were 13 CR and 18 PR among the 37 assessable children with HL (combined response rate, 84%; 95% CI, 68% to 94%). Although 59% courses were associated with grade IV neutropenia, treatment was well tolerated and without toxic deaths.
MIED is an effective regimen for refractory/recurrent childhood malignant lymphoma, permitting a bridge to intensification therapy with HSCT.
Annals of Oncology 02/2011; 22(2):468-71. · 6.43 Impact Factor
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C H Pui,
D Pei,
J T Sandlund,
R C Ribeiro,
J E Rubnitz,
S C Raimondi, M Onciu,
D Campana,
L E Kun,
S Jeha,
C Cheng,
S C Howard,
M L Metzger,
D Bhojwani,
J R Downing,
W E Evans,
M V Relling
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ABSTRACT: We analyzed the long-term outcome of 1011 patients treated in five successive clinical trials (Total Therapy Studies 11, 12, 13A, 13B, and 14) between 1984 and 1999. The event-free survival improved significantly (P=0.003) from the first two trials conducted in the 1980s to the three more recent trials conducted in the 1990s. Approximately 75% of patients treated in the 1980s and 80% in the 1990s were cured. Early intensive triple intrathecal therapy, together with more effective systemic therapy, including consolidation and reinduction treatment (Studies 13A and 13B) as well as dexamethasone (Study 13B), resulted in a very low rate of isolated central nervous system (CNS) relapse rate (<2%), despite the reduced use of cranial irradiation. Factors consistently associated with treatment outcome were age, leukocyte count, immunophenotype, DNA index, and minimal residual disease level after remission induction treatment. Owing to concerns about therapy-related secondary myeloid leukemia and brain tumors, in our current trials we reserve the use of etoposide for patients with refractory or relapsed leukemia undergoing hematopoietic stem cell transplantation, and cranial irradiation for those with CNS relapse. The next main challenge is to further increase cure rates while improving quality of life for all patients.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2009; 24(2):371-82. · 8.30 Impact Factor
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ABSTRACT: There has been a steady improvement in cure rates for children with advanced-stage lymphoblastic non-Hodgkin's lymphoma. To further improve cure rates whereas minimizing long-term toxicity, we designed a protocol (NHL13) based on a regimen for childhood T-cell acute lymphoblastic leukemia, which features intensive intrathecal chemotherapy for central -nervous system-directed therapy and excludes prophylactic cranial irradiation. From 1992 to 2002, 41 patients with advanced-stage lymphoblastic lymphoma were enrolled on the protocol. Thirty patients had stage III and 11 had stage IV disease. Thirty-three cases had a precursor T-cell immunophenotype, five had precursor B-cell immunophenotype and in three immunophenotype was not determined. Out of the 41 patients, 39 (95%) achieved a complete remission. The 5-year event-free rate was 82.9+/-6.3% (s.e.), and 5-year overall survival rate was 90.2+/-4.8% (median follow-up 9.3 years (range 4.62-13.49 years)). Adverse events included two induction failures, one death from typhlitis during remission, three relapses and one secondary acute myeloid leukemia. The treatment described here produces high cure rates in children with lymphoblastic lymphoma without the use of prophylactic cranial irradiation.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2009; 23(6):1127-30. · 8.30 Impact Factor
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S Jeha,
D Pei,
S C Raimondi, M Onciu,
D Campana,
C Cheng,
J T Sandlund,
R C Ribeiro,
J E Rubnitz,
S C Howard,
J R Downing,
W E Evans,
M V Relling,
C-H Pui
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ABSTRACT: To evaluate the impact of contemporary therapy on the clinical outcome of children with pre-B acute lymphoblastic leukemia (ALL) and the t(1;19)/TCF3/PBX1, we analyzed 735 patients with B-cell precursor ALL treated in four successive protocols at St Jude Children's Research Hospital. The 41 patients with the t(1;19) had a comparable event-free survival to that of the 694 patients with other B-cell precursor ALL (P=0.63; 84.2+/-7.1% (s.e.) vs 84.0+/-1.8% at 5 years). However, patients with the t(1;19) had a lower cumulative incidence of any hematological relapse (P=0.06; 0 vs 8.3+/-1.2% at 5 years) but a significantly higher incidence of central nervous system (CNS) relapse (P<0.001; 9.0+/-5.1% vs 1.0+/-0.4% at 5 years). In a multivariate analysis, the t(1;19) was an independent risk factor for isolated CNS relapse. These data suggest that with contemporary treatment, patients with the t(1;19) and TCF3/PBX1 fusion have a favorable overall outcome but increased risk of CNS relapse.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 03/2009; 23(8):1406-9. · 8.30 Impact Factor
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ABSTRACT: We report a patient with X-linked lymphoproliferative disease (XLP) who developed multiple central nervous system (CNS) manifestations of Epstein-Barr virus infection. XLP, or Duncan syndrome, is a rare inherited disorder characterized by the inability to clear Epstein-Barr virus infection. In addition to Epstein-Barr virus encephalitis, CNS lymphoproliferative disease, and lymphoma, this patient also developed MR angiographic evidence of diffuse fusiform aneurysmal dilation of intracranial vessels.
American Journal of Neuroradiology 05/2006; 27(4):884-6. · 2.93 Impact Factor
