Bassem I. Razzouk

Peyton Manning Children’s Hospital at St.Vincent

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Raul C. Ribeiro

St. Jude Children's Research Hospital

Jeffrey E. Rubnitz

St. Jude Children's Research Hospital

Ching‐Hon Pui

St. Jude Children's Research Hospital

John T. Sandlund

St. Jude Children's Research Hospital

Stanley Pounds

St. Jude Children's Research Hospital

Sima Jeha

St. Jude Children's Research Hospital

Melissa M. Hudson

St. Jude Children's Research Hospital

Nobuko Hijiya

Columbia University Irving Medical Center

Gertjan J.L. Kaspers

Princess Máxima Center

Susana C. Raimondi

St. Jude Children's Research Hospital

Cooperative Institutions

St. Jude Children's Research Hospital

214

University of Tennessee Health Science Center

112

University of Tennessee at Knoxville

Children's Hospital of Philadelphia

Children's Oncology Group

The University of Texas MD Anderson Cancer Center

Boston Children's Hospital

Children's Cancer Center

Johns Hopkins University

American University of Beirut Medical Center

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A phase II evaluation of thiotepa followed by other multiagent chemotherapy regimens in infants and young children with malignant brain tumors

Cancer (1995)

Bassem I. Razzouk Richard L. Heideman Henry S. Friedman Jesse J. Jenkins Larry E. Kun

Background. Chemotherapy may be used to delay the need for cranial irradiation in infants and young children with malignant central nervous system (CNS) tumors. The polyfunctional alkylator thiotepa (TT) possesses significant in vitro and in vivo activity in many central nervous system tumors. Before the introduction of a multiagent chemotherapy previously shown to be active in such tumors, thiotepa alone was evaluated in an upfront therapeutic window. Methods. Twenty young children with CNS tumors (19 newly diagnosed, 1 recurrent) were treated with two cycles of TT before response evaluation. Patients on thiotepa without disease progression went on to receive further chemotherapy consisting of alternating cycles of cyclophosphamide plus vincristine, cisplatin plus etoposide, and further TT. Patients with disease progression received radiation therapy. Results. Low objective rates of response and poor survival led to early study termination. Of 17 patients evaluable for response, 6 (35%) demonstrated disease progression during initial TT therapy. Only two objective responses were noted, both in patients with medulloblastoma. Among the 19 patients evaluable for survival, the overall and progression free survivals were 45% and 20%, respectively, at 3 years postdiagnosis. Myelosuppression was the dominant treatment-related toxicity. Conclusions. Although the numbers of patients were small, thiotepa as used in this study was associated with a poor objective response rate and an unacceptably high rate of disease progression. These results may be partly related to TT's significant myelosuppressive effects and the postponement of more effective chemotherapy. Cancer 1995;75:2762–7.

ThioTEPA

10.1002/1097-0142(19950601)75:11<2762::aid-cncr2820751121>3.0.co;2-2

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Citations (17)

Improved Remission Induction Rate of Childhood AML: Preliminary Results of the AML02 Trial.

Blood (2005)

Jeffrey E. Rubnitz Bassem I. Razzouk Paul Bowman Gary V. Dahl Norman J. Lacayo

Induction chemotherapy

Gemtuzumab ozogamicin

Minimal Residual Disease

Neoadjuvant Therapy

10.1182/blood.v106.11.275.275

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Citations (6)

Impact of age on outcome of pediatric acute myeloid leukemia

Cancer (2006)

Bassem I. Razzouk Elihu H. Estey Stanley Pounds Shelly Lensing Sherry Pierce

Abstract BACKGROUND The prognostic significance of age among pediatric patients with acute myeloid leukemia (AML) was investigated. METHODS The authors reviewed the outcome of 424 patients who were ≤21 years of age at the time of diagnosis of AML (excluding acute promyelocytic leukemia) between 1983 and 2002 at St. Jude Children's Research Hospital ( n = 288) or the M. D. Anderson Cancer Center ( n = 136). Two treatment eras (1983‐1989 and 1990‐2002) were examined because of the greater intensity of treatment during the recent era. RESULTS After controlling for the effects of cytogenetics, white blood cell (WBC) count, French–American–British (FAB) subtype, and treatment era, they observed that age and treatment era interacted significantly in relation to event‐free survival (EFS) ( P = .033). Patients 10 years of age or older were at greater risk of an adverse event than younger patients in the recent era (hazard ratio = 1.8; 95% confidence interval [CI]: 1.3‐2.6; P = .005) but not in the early era. The rate of adverse events (death or recurrence) increased significantly with each year of age in the recent era (4.3%/year; 95% CI: 1.9‐6.8%; P = .001) but not in the early era. The rate of death increased significantly with each year of age in both eras (4.4%/year; 95% CI: 2.3‐6.5%; P <.001). EFS and survival showed no association with study site, and the effects of age were similar at the 2 sites. CONCLUSIONS These results suggest that age is an independent prognostic factor in childhood AML and that children younger than 10 years benefit more than older children from newer intensive therapies. Cancer 2006. © 2006 American Cancer Society.

White blood cell

10.1002/cncr.21892

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Citations (58)

The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

Haematologica (2014)

Ursula Creutzig Martin Zimmermann Michael Dworzak B Gibson R. Y. J. Tamminga

The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P

10.3324/haematol.2014.104182

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Citations (46)

Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer

Pediatric Blood & Cancer (2005)

Burgess B. Freeman Pamela S. Hinds Lisa Iacono Bassem I. Razzouk Elizabeth Burghen

Abstract Background Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy. Procedure Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods. Results Twelve children participated; six (median age 15.2 years; range 9.3–18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC 0–24 and clearance (CL) were 67.1 IU/ml·hr (13.8–102.6) and 0.26 L/hr/m 2 (0.19–1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC 0–24 and CL of EPO was 126.5 IU/ml·hr (107.3–161.1) and 0.21 L/hr/m 2 (0.15–0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects. Conclusions EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects. Pediatr Blood Cancer 2006; 47:572–579. © 2005 Wiley‐Liss, Inc.

Pharmacodynamics

Epoetin alfa

10.1002/pbc.20685

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Citations (9)

Phase II Trials of Clofarabine in Relapsed or Refractory Pediatric Leukemia.

Blood (2004)

Sima Jeha Bassem I. Razzouk Michael Rytting Paul S. Gaynon Richard Kadota

Clofarabine

Refractory (planetary science)

Nucleoside analogue

10.1182/blood.v104.11.684.684

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Citations (13)

Reinduction of relapsed acute promyelocytic leukemia with ATRA and low dose antimetabolite‐based chemotherapy

Pediatric Blood & Cancer (2005)

Christopher C. Dvorak Robert P. Sanders Gary V. Dahl Sarah S. Donaldson Bassem I. Razzouk

Abstract While the disease‐free survival of acute promyelocytic leukemia (APML) now approaches 75%, some children continue to experience relapses, and questions remain as to the optimal management of these patients. We describe two young children who experienced combined relapses in the bone marrow and extramedullary locations following hematopoietic stem cell transplantation (HSCT). An induction regimen, consisting of all‐trans retinoic acid (ATRA), methotrexate, and 6‐mercaptopurine (6MP), successfully and safely achieved hematologic remission in one patient and molecular remission in the other. These cases demonstrate that there is a role for ATRA plus differentiating chemotherapy other than arsenic trioxide in the treatment of relapsed APML. Pediatr Blood Cancer 2007;48:582–585. © 2005 Wiley‐Liss, Inc.

Arsenic Trioxide

Blood cancer

Regimen

10.1002/pbc.20592

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Citations (11)

Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia

Blood (2000)

Amar Gajjar Patricia Harrison John T. Sandlund Gaston K. Rivera Raul C. Ribeiro

Acute lymphocytic leukemia

10.1182/blood.v96.10.3381

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