Publications by authors named "Bassem I Razzouk"

50 Publications

Typhlitis in childhood cancer.

Cancer 2005 Jul;104(2):380-7

Division of Diagnostic Imaging, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. [email protected] jude.org

Background: Typhlitis is increasingly recognized in children undergoing chemotherapy but is poorly characterized. The authors investigated the demographic, clinical, and imaging (ultrasonography and computed tomography [CT] scans) variables related to the diagnosis, risk, and outcome of typhlitis.

Methods: The authors reviewed the records of patients who had typhlitis (bowel wall thickness > or = 0.3 cm plus clinical findings) during treatment at St. Jude Children's Research Hospital (Memphis, TN) between 1990 and 2001. They assessed whether duration of typhlitis was related to bowel wall thickness, extent of colonic involvement, ascites, demographics, primary diagnosis, symptoms of typhlitis, or duration of neutropenia. To identify risk factors for typhlitis, the authors compared the demographic data and previous drug therapy of 78 patients who had typhlitis and 1231 identically treated children who did not.

Results: Of 3171 children, 83 (2.6%) developed typhlitis. Frequent symptoms were abdominal pain (91%), fever (84%), abdominal tenderness (82%), and diarrhea (72%). Twelve percent of the patients were not neutropenic. Duration of typhlitis was associated with bowel wall thickness measured by ultrasonography (n = 68; P = 0.05) but not CT scan (n = 48; P = 0.67) and was associated with duration of neutropenia (P = 0.02), fever (P = 0.01), and abdominal tenderness (P = 0.04). Age >16 years at cancer diagnosis was the only demographic factor associated with typhlitis (P = 0.03). Two patients died of typhlitis.

Conclusions: Ultrasonography was a useful imaging modality for children with suspected typhlitis. The classic triad of abdominal pain, fever, and neutropenia may be absent. The severity of typhlitis was related to the duration of neutropenia and the presence of fever or abdominal tenderness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.21134DOI Listing
July 2005

Cancer-related deaths in children and adolescents.

J Palliat Med 2005 Feb;8(1):86-95

Baptist Memorial Hospital-East, Memphis, Tennessee, USA.

Background: To add to the data regarding the quality of care given to dying children and their families.

Objective: To develop baseline of end-of-life care at a single pediatric facility to evaluate institution-wide palliative care initiative.

Design: Retrospective chart review of all known deaths during an 18-month time period.

Setting/subjects: One hundred forty-five charts of patients from a single pediatric cancer facility who died during designated time period.

Measurements: Variables included: cause and place of death; CPR/DNR status prior to death; length of end of life care prior to death; sibling counseling and bereavement counseling offered to family after death; and wishes or preferences of patient/family regarding the death experience.

Results: Results included: solid tumor patients more likely to die of progressive disease than leukemia or bone marrow transplant patients; bone marrow transplant patients 2-3 times more likely to die of cardiopulmonary or cardiovascular complications; solid tumor patients were more likely to die at home than leukemia patients; solid tumor/brain tumor patients had a median time in end of life or palliative care of 29 days compared to leukemia patients' median of 11 days; 48% of DNRs completed 11 days prior to death.

Conclusions: Relationship exists between diagnosis, cause and place of death in this population; findings replicate findings of 4 similar studies; accurate and consistent quality standards of care need to be established for this population as well as methods of documentation before reviewing/accrediting agencies impose standards that are not evidence based.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jpm.2005.8.86DOI Listing
February 2005

Clinical presentation and treatment outcome of children with Burkitt lymphoma in Lebanon: a single institution's experience.

J Pediatr Hematol Oncol 2004 Nov;26(11):749-53

Children's Cancer Center of Lebanon, American University of Beirut, Lebanon.

The authors reviewed the medical records of 42 children younger than 13 years of age diagnosed with Burkitt lymphoma at the American University of Beirut Medical Center between 1983 and 1993. The male:female ratio was 3.9. The abdomen was the most common site of disease (86%). Jaw, central nervous system, and bone marrow involvement occurred in 16.6%, 16.6%, and 9.5%, respectively. The mean LDH level was 447 U/L. The mean age at diagnosis was 6.9 years. Thirty-nine patients received a variation of the COMP protocol. The total duration of treatment ranged from 6 to 18 months. At a median follow-up of 5 years the event-free survival was 100% for children with stages I and II disease, 77.4% (+/- 2 SE) for stage III, and 0% for stage IV. Failures in stage III patients were due to tumor lysis (3/24) and progressive disease (2/24). Aggressive therapy with high doses of methotrexate and anthracyclines may not be necessary for the treatment of children with extensive abdominal disease (stage III) in Lebanon. If confirmed in a larger series of patients, this study could have a major impact on the treatment of Burkitt lymphoma in Lebanon and other countries with limited resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00043426-200411000-00012DOI Listing
November 2004

Death during induction therapy and first remission of acute leukemia in childhood: the St. Jude experience.

Cancer 2004 Oct;101(7):1677-84

Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.

Background: Despite improvements in supportive care, death due to treatment toxicity remains a significant problem for children treated for acute leukemia.

Methods: To determine the causes of and risk factors for death unrelated to refractory leukemia, to disease recurrence, or to second malignancy, the authors reviewed the records of 1011 patients with acute lymphoblastic leukemia (ALL) and 260 patients with acute myeloid leukemia (AML) treated between 1984 and 1999 and between 1983 and 2002, respectively, at St. Jude Children's Research Hospital (Memphis, TN). Data for patients who underwent stem cell transplantation were censored at the time of transplantation.

Results: For patients with ALL, the estimated 10-year cumulative incidence of death was 2.9% +/- 5.3%. Age was the only predictor of death. Patients with ALL 1-9 years old had a significantly lower risk of death than did younger or older patients (P = 0.002). For patients with AML, the estimated 5-year cumulative incidence of death was 7.6% +/- 1.9%. Increasing age and increasing leukocyte count were significantly associated with increased risk of death. For patients with ALL and with AML, the incidence of death remained relatively constant during the time periods studied. Infection was the most common cause of death.

Conclusions: In the current study, the authors determined that children > or = 10 years of age are at increased risk of death during therapy for ALL and AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.20532DOI Listing
October 2004

Severe cardiopulmonary complications consistent with systemic inflammatory response syndrome caused by leukemia cell lysis in childhood acute myelomonocytic or monocytic leukemia.

Pediatr Blood Cancer 2005 Jan;44(1):63-9

Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.

Background: Life-threatening pulmonary complications that coincide with cell lysis during early chemotherapy and that mimic systemic inflammatory response syndrome (SIRS) have been reported in patients with acute myeloid leukemia (AML).

Methods: We reviewed the records of patients with de novo AML, excluding M3 and Down syndrome, treated at our institution between 1991 and 2002 to determine the prevalence of severe SIRS with grade 3/4 pulmonary complications and to identify AML subtypes associated with severe SIRS. To examine the role of cell lysis, we compared leukocyte reduction in AML subtypes affected by severe SIRS with that in unaffected subtypes.

Results: Of 155 patients, 5 (3 with M4eo and 2 with M5) experienced severe pulmonary complications attributed to tumor lysis, met the criteria for severe SIRS, and showed no clear evidence of infection. Four required pressor support for severe hypotension. Severe SIRS was significantly more common in myelomonocytic or monocytic AML (M4/M4eo/M5) than in other subtypes (P = 0.010) and significantly more common in M4eo than in M4/M5 (P = 0.008). Among 112 cases for which information was available, leukocyte reduction was significantly greater in patients with M4/M4eo/M5 than among others during the first 4 days of chemotherapy (P = 0.015). Leukocyte reduction was significantly more rapid among patients who had severe SIRS than among others (P = 0.008).

Conclusions: Patients with M4/M4eo/M5 AML, especially M4eo, experience life-threatening cardiopulmonary complications of tumor lysis that meet the criteria for severe SIRS. This observation may reflect more rapid cell reduction and the unique biology of this subtype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.20192DOI Listing
January 2005

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital.

Blood 2004 Nov 13;104(9):2690-6. Epub 2004 Jul 13.

Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 x 10(9)/L or more, or CNS-3 (5 or more leukocytes/microL with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lower-risk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% +/- 2.6% (SE); the 8-year rate was 78.6% +/- 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% +/- 0.8%, and that of isolated plus combined CNS relapse was 3.0% +/- 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% +/- 1.3% in the lower-risk patients who received a cumulative dose of 1.2 g/m(2) and 5.0% +/- 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m(2) (P = .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2004-04-1616DOI Listing
November 2004

Phase II trial of cladribine and cytarabine in relapsed or refractory myeloid malignancies.

Leuk Res 2004 Apr;28(4):349-52

Department of Hematology-Oncology, St. Jude Children's Research Hospital, Mail Stop 260, 332 N. Lauderdale Street, Memphis, TN 38105-2794, USA.

To evaluate the efficacy of cladribine and cytarabine in children with relapsed or refractory myeloid malignancies, we administered cytarabine (200 mg/m2 per day) by continuous subcutaneous infusion and cladribine (8.9 mg/m2 per day) by continuous intravenous infusion concomitantly for 5 days to nine patients younger than 21 years. After one course, five patients had no response, two patients had partial responses, one had stable disease, and one had progressive disease. Two patients received a second course: one patient had stable disease after one course and progressive disease after the second; another patient had a partial response after one course and no response after the second. Despite the efficacy of the cladribine and cytarabine regimen in treating newly diagnosed acute myeloid leukemia (AML) in a previously reported study, the combination was not effective for relapsed or refractory childhood AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2003.08.010DOI Listing
April 2004

Results of therapy for acute lymphoblastic leukemia in black and white children.

JAMA 2003 Oct;290(15):2001-7

Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

Context: Treatment results for acute lymphoblastic leukemia (ALL) clearly have improved over the past decade, but black children have not fared as well as white children in large national trials.

Objective: To compare the clinical outcomes of therapy for black and white children with ALL treated at a single institution.

Design, Setting, And Patients: A retrospective analysis of 412 children and adolescents (68 black, 338 white, and 6 other race) with newly diagnosed ALL who were treated consecutively at a pediatric cancer center in Memphis, Tenn. Patients were enrolled from December 1991 to July 1998 in successive Total Therapy studies regardless of race, ethnicity, or ability to pay and received risk-directed therapy according to stringent criteria.

Interventions: All patients received the same intensive, remission-induction therapy followed by 120 weeks of risk-assigned postremission therapy that included reinduction treatment, pulses of high-dose methotrexate, and early intensification of intrathecal chemotherapy.

Main Outcome Measures: Event-free and overall survival rates for black and white children were estimated by the method of Kaplan and Meier and compared with the Mantel-Haenszel test and by Cox proportional hazards regression analysis, adjusting for known prognostic factors.

Results: The 68 black children were significantly more likely than the 338 white children to have higher-risk prognostic features, including an initial leukocyte count greater than 100 x 10(3)/ microL, a T-cell immunophenotype, and the t(1;19) chromosomal translocation with E2A-PBX1 fusion, and were less likely to have hyperdiploid blast cells, a favorable prognostic factor in childhood ALL. However, the clinical outcomes for these 2 cohorts were not significantly different: 5-year event-free and overall survival rates were 80.7% (95% confidence interval [CI], 70.3%-91.1%) and 86.2% (95% CI, 77.2%-95.2%) for black children vs 79.4% (95% CI, 74.7%-84.1%) and 85.0% (95% CI, 80.9%-89.1%) for white children. Ten-year results also were comparable, but the CIs were wide because of the small numbers of patients who had been followed up for 10 years or more. The lack of a racial effect on the long-term outcome of therapy was still apparent in a multivariate Cox regression analysis, adjusting for sex, age, presenting leukocyte count, leukemic cell DNA index, immunophenotype, and central nervous system status.

Conclusion: With equal access to effective antileukemic therapy, black and white children with ALL can expect the same high rate of cure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.290.15.2001DOI Listing
October 2003

Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia.

Br J Haematol 2003 Oct;123(2):243-52

Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.

In children with acute myeloid leukaemia (AML), morphological and karyotypic studies cannot precisely assess response to treatment, and less than one-third of patients have genetic markers for molecular studies of residual disease. We determined the usefulness of a four-colour flow cytometric strategy developed in our laboratory to study residual disease. We first compared the immunophenotypes of AML cells obtained from 54 children at diagnosis with those of cells from 59 normal or regenerating bone marrow samples. Forty-six of the 54 AML cases (85.2%) had immunophenotypes that allowed detection of 0.1-0.01% residual leukaemic cells. Of 230 bone marrow samples obtained from those 46 patients during and off treatment, 61 (26.5%) had >/= 0.1% AML cells by flow cytometry. We found that core binding factor-associated AML had a significantly better early treatment response. Mean (+/- standard error) 2-year survival estimate was 33.1 +/- 19.1% for patients with >/= 0.1% AML cells by flow cytometry after induction therapy, but 72.1 +/- 11.5% for those with < 0.1% AML cells (P = 0.022); overt recurrence of AML within the subsequent 6 months was significantly more likely in the former group. The assay described here holds promise for guiding the choice of post-remission treatment options in children with AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1046/j.1365-2141.2003.04610.xDOI Listing
October 2003

Viridans streptococcal sepsis: clinical features and complications in childhood acute myeloid leukemia.

J Pediatr Hematol Oncol 2003 Sep;25(9):696-703

Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

Purpose: Treatment of acute myeloid leukemia (AML) is associated with substantial adverse effects, including neutropenia and infection. Viridans streptococci (VS) are a primary cause of infection and pneumonia in patients with neutropenia. The authors determined the incidence, clinical features, and complications of VS sepsis in children receiving chemotherapy for AML.

Methods: The authors retrospectively reviewed the records of 172 patients treated on their institutional protocols AML91 (n = 95) and AML97 (n = 77) and identified 36 patients who had VS sepsis.

Results: The 1-year cumulative incidence of VS sepsis was significantly higher in AML97 than in AML91. Patients with favorable cytogenetic features (ie, t(9;11), t(8;21), or inv(16)) had a significantly higher incidence of infection than did other patients. VS sepsis developed at various times after chemotherapy was initiated, and patients remained febrile for a median of 15 days. Twelve patients (33%) experienced hypotension, 10 (28%) acute respiratory distress syndrome, and 6 (17%) fungal infection. Twenty-three patients (64%) required intensive care, 21 (58%), oxygen therapy, and 7 (19%), vasopressor medications. One patient died of pulmonary aspergillosis after VS sepsis. The 3-year cumulative incidence of aspergillosis was higher in patients with VS sepsis than in those without.

Conclusions: Although antibiotic therapy rapidly resolved VS sepsis, complications associated with this infection remained life-threatening in children receiving chemotherapy for AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00043426-200309000-00005DOI Listing
September 2003

Pathophysiology-directed therapy for acute hypoxemic respiratory failure in acute myeloid leukemia with hyperleukocytosis.

J Pediatr Hematol Oncol 2003 Jul;25(7):569-71

Division of Critical Care Medicine, St. Jude Children's Research Hospital, 332 N. Lauderdale, MS# 323, Memphis, TN 38105, U.S.A.

A 17-year-old with acute myeloid leukemia M4 and hyperleukocytosis developed fulminant hypoxemic respiratory failure at presentation. After failing to respond to conventional mechanical ventilation and leukapheresis, he was started on inhaled nitric oxide (iNO) with dramatic improvement in oxygenation. Following graduated chemotherapy, his pulmonary status again deteriorated coincident with tumor lysis. After failing to respond to increases in iNO, he was placed in prone position with immediate improvement. The patient was successfully extubated. Patients with myelomonocytic leukemias are at risk for early death due to pulmonary complications. The use of adjuvant therapies directed by specific pathophysiology might decrease this risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00043426-200307000-00015DOI Listing
July 2003

Pharmacokinetics of 2-chlorodeoxyadenosine in a child undergoing hemofiltration and hemodialysis for acute renal failure.

J Pediatr Hematol Oncol 2002 Nov;24(8):677-80

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA.

The clearance of 2-chlorodeoxyadenosine (2-CdA) in patients with renal insufficiency has not been characterized previously. The authors describe the clinical course and the pharmacokinetics of 2-CdA in a child with acute monoblastic leukemia who experienced acute renal failure during treatment with cytarabine and 2-CdA. 2-CdA (9 mg/m per day) was infused over 30 minutes daily for 5 days. Plasma and dialysate concentrations of 2-CdA were measured by high-performance liquid chromatography. The rate of this patient's 2-CdA clearance was lower than the rates reported for children with normal renal function. The average clearance rate, reflecting systemic clearance and clearance by continuous venovenous hemofiltration and hemodialysis, was 12.4 L/hour per m for the first 3 days of 2-CdA therapy. He did not experience untoward hematologic toxicity. Because high 2-CdA plasma concentrations were observed in this patient, clinicians are advised to exercise caution when using this drug in patients with renal dysfunction. More experience in the administration of 2-CdA to patients with renal insufficiency will be necessary to determine the need for dosage adjustment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00043426-200211000-00016DOI Listing
November 2002

Risk factors for traumatic and bloody lumbar puncture in children with acute lymphoblastic leukemia.

JAMA 2002 Oct 23-30;288(16):2001-7

Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.

Context: Traumatic or bloody lumbar puncture (LP) reduces the diagnostic value of the procedure and may worsen the outcome of patients with acute lymphoblastic leukemia (ALL). Little is known about the risk factors for traumatic and bloody LP.

Objectives: To determine the risk factors for traumatic and bloody LP.

Design, Setting, And Patients: Retrospective cohort study of 956 consecutive patients with newly diagnosed childhood ALL who were treated at a pediatric cancer center between February 1984 and July 1998.

Interventions: All patients underwent a diagnostic LP followed by a median of 4 LPs to instill intrathecal chemotherapy.

Main Outcome Measure: Traumatic LP was defined as an LP in which cerebrospinal fluid contained at least 10 red blood cells (RBCs) per microliter and bloody LP as one in which the cerebrospinal fluid contained at least 500 RBCs per microliter.

Results: Of the 5609 LPs evaluated, 1643 (29%) were traumatic and 581 (10%) were bloody. The estimated odds ratios (ORs) and 95% confidence intervals (CIs) for traumatic LP were 1.5 (95% CI, 1.2-1.8) for black vs white race, 2.3 (95% CI, 1.7-3.0) for age younger than 1 year vs 1 year or older, 1.4 (95% CI, 1.2-1.7) for early vs recent (dedicated procedure area and general anesthesia) treatment era, 1.5 (95% CI, 1.2-1.8) for platelet count of 100 x 10(3)/ microL or more vs less than 100 x 10(3 )/ microL, 10.8 (95% CI, 7.7-15.2) for short (1 day) vs longer (>15 days) interval since the previous LP, and 1.4 (95% CI, 1.1-1.8) for the least vs the most experienced practitioners. Analyses for bloody LP yielded similar results.

Conclusions: The unmodifiable risk factors for traumatic and bloody LP include black race, age younger than 1 year, a traumatic or bloody previous LP performed within the past 2 weeks, and a previous LP performed when the platelet count was 50 x 10(3)/ microL or less. Modifiable risk factors include procedural factors reflected in treatment era, platelet count of 100 x 10(3)/ microL or less, an interval of 15 days or less between LPs, and a less experienced practitioner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.288.16.2001DOI Listing
November 2002

Interim comparison of a continuous infusion versus a short daily infusion of cytarabine given in combination with cladribine for pediatric acute myeloid leukemia.

J Clin Oncol 2002 Oct;20(20):4217-24

Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Purpose: To identify the optimal schedule for infusion of cytarabine (ara-C) given with cladribine (2-CdA) to pediatric patients with acute myeloid leukemia (AML), and to compare the effects of the two schedules on the pharmacokinetics of ara-C triphosphate (ara-CTP) in leukemic cells.

Patients And Methods: Forty-nine pediatric patients with newly diagnosed primary AML received a 5-day course of ara-C 500 mg/m(2)/d and 2-CdA 9 mg/m(2)/d. They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a continuous infusion (arm B). Cellular pharmacokinetics were studied on days 1 and 2. All patients then received two courses of remission induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV).

Results: Thirty-two percent of patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered complete remission (P =.045) after ara-C and 2-CdA therapy. Coadministration of 2-CdA increased the intracellular concentration of ara-CTP in 20 of 36 patients, although we found no statistically significant difference between the treatment arms in this effect (P =.63). The incidence of toxicity did not differ significantly between the two treatment arms (P =.53). After two courses of DAV, the rate of complete remission was 91% in arm A and 96% in arm B (P =.58).

Conclusion: Intracellular accumulation of ara-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this effect were seen. The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2002.10.006DOI Listing
October 2002

Skeletal manifestations of pediatric acute megakaryoblastic leukemia.

J Pediatr Hematol Oncol 2002 Oct;24(7):561-5

Division of Hematology/Oncology, McMaster University Medical Center, Hamilton, Ontario, Canada.

Once considered rare, acute megakaryoblastic leukemia (AMKL) now accounts for about 12% of all cases of de novo acute myeloid leukemia in children. Most cases of AMKL are difficult to diagnose because of their complex clinical presentation and unusual bone marrow morphologic features. In children, AMKL is often confused with metastatic solid tumors or myelodysplastic syndrome. Between January 1984 and December 1999, 43 patients were diagnosed with childhood AMKL at the authors' institution. Five of these presented with unusual skeletal lesions. These abnormalities (bilaterally symmetrical periostitis and osteolytic lesions) differed markedly from those commonly reported in association with pediatric acute leukemias. The authors present their experience and review the literature to define the spectrum of bony involvement associated with AMKL. This report will contribute to the evolving clinical characterization of this entity and increase clinicians' and radiologists' awareness of the manifestations of AMKL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00043426-200210000-00014DOI Listing
October 2002

The majority of children and adolescents with acute myeloid leukemia have detectable anti-DT388-GMCSF IgG concentrations, but at concentrations that should not preclude in vivo activity.

J Pediatr Hematol Oncol 2002 Oct;24(7):521-6

Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston 29425, USA.

Purpose: As a novel approach for the treatment of acute myeloid leukemia (AML), the authors are developing a fusion toxin (DT(388)-GMCSF) consisting of a truncated diphtheria toxin (DT(388)) linked to human granulocyte-macrophage colony-stimulating factor (GMCSF). A critical step in the development of DT(388)-GMCSF for clinical use in childhood and adolescent AML is to determine whether children and adolescents have preexisting antibodies to DT(388)-GMCSF due to childhood immunizations against diphtheria toxoid.

Patients And Methods: Sera from 33 children and adolescents with AML and one with juvenile myelomonocytic leukemia were collected. The median age was 11.8 years. All scheduled diphtheria toxoid vaccinations were current except for the child diagnosed at 4 months of age. Anti-DT(388)-GMCSF antibody concentrations were detected by an enzymoimmunoassay and by an in vitro bioassay.

Results: Thirty of 34 (88%) children and adolescents had detectable anti-DT(388)-GMCSF IgG antibody concentrations. The median concentration was 1.5 microg/mL, with a range from undetectable to 191.4 microg/mL. There was a positive correlation between the enzymoimmunoassay and bioassay. There was no difference between the anti-DT(388)-GMCSF IgG concentrations in these children and adolescents with AML and in 43 adults with AML. Preliminary results of the phase 1 trial of DT -GMCSF in adults with AML indicate that patients with baseline anti-DT(388)-GMCSF IgG concentrations of less than 2 microg/mL can achieve circulating DT(388)-GMCSF concentrations and can exhibit antileukemic activity. Twenty-three of 34 (67.6%) children and adolescents had anti-DT(388)-GMCSF IgG concentrations less than 2 microg/mL.

Conclusions: Despite routine diphtheria toxoid vaccinations, most children and adolescents with AML do not have anti-DT -GMCSF IgG concentrations that preclude in vivo activity of DT -GMCSF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00043426-200210000-00005DOI Listing
October 2002

Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia.

Blood 2002 Oct;100(7):2399-402

Departments of Hematology-Oncology, Biostatistics, and Pathology, St Jude Children's Research Hospital, and the University of Tennessee, Memphis TN 38105-2794, USA.

In children with acute lymphoblastic leukemia (ALL), response to treatment is assessed by bone marrow aspiration. We investigated whether minimal residual disease (MRD) can be effectively monitored in peripheral blood. We used flow cytometric techniques capable of detecting 1 leukemic cell among 10 000 or more normal cells to compare MRD measurements in 718 pairs of bone marrow and peripheral blood samples collected from 226 children during treatment for newly diagnosed ALL. MRD was detected in marrow and blood in 72 pairs and in marrow but not in blood in 67 pairs; it was undetectable in the remaining 579 pairs. Remarkably, findings in marrow and blood were completely concordant in the 150 paired samples from patients with T-lineage ALL: for each of the 35 positive marrow samples, the corresponding blood sample was positive. In B-lineage ALL, however, only 37 of 104 positive marrow samples had a corresponding positive blood sample. Notably, peripheral blood MRD in these patients was associated with a very high risk for disease recurrence. The 4-year cumulative incidence of relapse in patients with B-lineage ALL was 80.0% +/- 24.9% for those who had peripheral blood MRD at the end of remission induction therapy but only 13.3% +/- 9.1% for those with MRD confined to the marrow (P =.007). These results indicate that peripheral blood may be used to monitor MRD in patients with T-lineage ALL and that peripheral blood MRD may provide strong prognostic information in patients with B-lineage ALL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2002-04-1130DOI Listing
October 2002

Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia.

Blood 2002 Jul;100(1):52-8

Department of Hematology-Oncology, St Jude Children's Research Hospital and the University of Tennessee, Memphis, TN 38105, USA.

Early clearance of leukemic cells is a favorable prognostic indicator in childhood acute lymphoblastic leukemia (ALL). However, identification of residual leukemic cells by their morphologic features is subjective and lacks sensitivity. To improve estimates of leukemia clearance, we applied flow cytometric techniques capable of detecting 1 leukemic cell in 10,000 or more normal cells and prospectively measured residual leukemia in bone marrow samples collected on day 19 of remission-induction chemotherapy from 248 children with newly diagnosed ALL. In 134 samples (54.0%), we identified at least 0.01% leukemic cells (0.01%-< 0.1% in 51 samples [20.6%], 0.1%-< 1% in 36 [14.5%], and > or = 1% in 47 [19.0%]). Among 110 children treated within a single chemotherapy program, the 5-year mean +/- SE cumulative incidence of relapse or failure to achieve remission was 32.2% +/- 6.5% for the 59 patients with 0.01% residual leukemic cells or greater on day 19 and 6.0% +/- 3.4% for the 51 patients with less than 0.01% leukemic cells (P <.001). The prognostic value of day-19 bone marrow status defined by flow cytometry was superior to that defined by morphologic studies and remained significant after adjustment for other clinical and biologic variables. Lack of detectable leukemic cells on day 19 was more closely associated with relapse-free survival than was lack of detectable residual disease at the end of remission induction (day 46). Thus, approximately half of the children with ALL achieve profound clearance of leukemic cells after 2 to 3 weeks of remission-induction chemotherapy, and these patients have an excellent treatment outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2002-01-0006DOI Listing
July 2002

Favorable impact of the t(9;11) in childhood acute myeloid leukemia.

J Clin Oncol 2002 May;20(9):2302-9

Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

Purpose: To determine the impact of MLL rearrangements on the outcome of children with acute myeloid leukemia (AML).

Patients And Methods: We analyzed the clinical and biologic features of 298 infants and children with primary AML treated on four consecutive institutional clinical trials. The Kaplan-Meier method was used in survival analysis and the Cox proportional-hazards model was used to analyze the effect of potential prognostic factors on event-free survival (+/- 1 SE).

Results: Molecular studies of 152 cases detected 42 with MLL rearrangements. The karyotypes of these 42 revealed the t(9;11) (15 cases), abnormalities of chromosomes 10 and 11 (nine cases), the t(11;19) (four cases), other abnormalities of 11q23 (seven cases), and miscellaneous rearrangements (seven cases). Among these 42 patients, the 15 whose leukemic cells carried the t(9;11) had a better outcome (66% +/- 15%) than the other 27 (25.9% +/- 11.2%; P =.004). Cases with the t(9;11) were also characterized by M5 AML morphology (21 of 23 cases). Of the 63 patients with M5 AML, the 21 whose leukemic cells demonstrated the t(9;11) had a better outcome (71.1% +/- 11%) than the other 42 (25.8% +/- 7.9%; P =.0004). The only independent factors indicating a favorable prognosis were presenting leukocyte count less than 50 x 10(9)/L (relative risk of relapse, 0.73; 95% confidence interval, 0.55 to 0.97; P =.03) and the t(9;11) (relative risk of relapse, 0.32; 95% confidence interval, 0.16 to 0.64; P =.002).

Conclusion: We conclude that the t(9;11) is the most favorable genetic factor for patients with AML treated at our institution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2002.08.023DOI Listing
May 2002

A defective, rearranged Epstein-Barr virus genome in EBER-negative and EBER-positive Hodgkin's disease.

Am J Pathol 2002 Mar;160(3):781-6

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.

A ubiquitous herpesvirus that establishes life-long infection, the Epstein-Barr virus (EBV) has yielded little insight into how a single agent in general accord with its host can produce diverse pathologies ranging from oral hairy leukoplakia to nasopharyngeal carcinoma, from infectious mononucleosis to Hodgkin's disease (HD) and Burkitt's lymphoma. Its pathogenesis is further confounded by the less than total association of virus with histologically similar tumors. In other viral systems, defective (interfering) viral genomes are known to modulate outcome of infection, with either ameliorating or intensifying effects on disease processes initiated by prototype strains. To ascertain whether defective EBV genomes are present in HD, we examined paraffin-embedded tissue from 56 HD cases whose EBV status was first determined by cytohybridization for nonpolyadenylated EBV RNAs (EBERs). Using both standard polymerase chain reaction (PCR) and PCR in situ hybridization, we successfully amplified sequences that span abnormally juxtaposed BamHI W and Z fragments characteristic of defective heterogeneous (het) EBV DNA from 10 of 32 (31%) EBER-positive tumors. Of 24 EBER-negative HD, 8 yielded PCR products indicating presence of het EBV DNA. Two of these contained defective EBV in the apparent absence of the prototype virus. Of the 42 tumors analyzed for defective EBV by both PCR techniques, there was concordance of results in 38 (90%). Detection of defective EBV genomes with the potential to disrupt viral gene regulation suggests one mechanism for pathogenic diversity that may also account for loss of prototypic EBV from individual tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867161PMC
http://dx.doi.org/10.1016/S0002-9440(10)64900-0DOI Listing
March 2002
-->