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Biomedical subjects

C A Hurwitz

Publications and source records attributed to C A Hurwitz.

At least 19 recordsLinked to original sources
PubMed2001

Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases.

PURPOSE: To develop more effective chemotherapy regimens for childhood acute myelogenous leukemia (AML). PATIENTS AND METHODS: Between June 1991 and December 1996, we administered the nucleoside analog 2-chlorodeoxyadenosine (2-CDA) to 73 children with primary AML and 20 children with secondary AML or myelodysplastic syndrome (MDS). Patients received one or two 5-day courses of 2-CDA (8.9 mg/m(2)/d) given by continuous infusion. All patients then received one to three courses of daunomycin, cytarabine, and etoposide (DAV) remission induction therapy. RESULTS: Seventy-two patients with primary AML were assessable for response. Their rate of complete remission (CR) was 24% after one course of 2-CDA, 40% after two courses of 2-CDA, and 78% after DAV therapy. Of the 57 patients who entered CR, 11 subsequently underwent allogeneic bone marrow transplantation (BMT), and 40 underwent autologous BMT. Twenty-nine patients remain in continuous CR after BMT. Two patients remain in CR after chemotherapy only. The 5-year event-free survival (EFS) estimate was 40% (SE = 0.080%). Patients with French-American-British (FAB) M5 AML had a higher rate of CR after treatment with 2-CDA (45% after one course and 70.6% after two courses) than did others (P =.002). In contrast, no patient with FAB M7 AML (n = 10) entered CR after treatment with 2-CDA. Similarly, no patient with primary MDS (n = 6) responded to 2-CDA. Seven patients with secondary AML or MDS (n = 14) had a partial response to one course of 2-CDA. CONCLUSION: This agent was well tolerated, and its toxicity was acceptable. Future trials should examine the effectiveness of 2-CDA given in combination with other agents effective against AML.

Adolescent↗
PubMed2001

Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01.

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium Protocol 91-01 was designed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity. Compared with prior protocols, post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks. Between 1991 and 1995, 377 patients (age, 0-18 years) were enrolled; 137 patients were considered standard risk (SR), and 240 patients were high risk (HR). Following a 5.0-year median follow-up, the estimated 5-year event-free survival (EFS) +/- SE for all patients was 83% +/- 2%, which is superior to prior DFCI ALL Consortium protocols conducted between 1981 and 1991 (P =.03). There was no significant difference in 5-year EFS based upon risk group (87% +/- 3% for SR and 81% +/- 3% for HR, P =.24). Age at diagnosis was a statistically significant prognostic factor (P =.03), with inferior outcomes observed in infants and children 9 years or older. Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase (P <.01, both univariate and multivariate). Older children (at least 9 years of age) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase (P <.01). Treatment on Protocol 91-01 significantly improved the outcome of children with ALL, perhaps due to the prolonged asparaginase intensification and/or the use of dexamethasone. The inferior outcome of older children may be due, in part, to increased intolerance of intensive therapy.

Adolescent↗
PubMed2000

Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia.

BACKGROUND: The authors report the occurrence of fatal or near-fatal sepsis in 16 of 38 children with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a new induction regimen that differed from its predecessor by the substitution of dexamethasone for prednisone. METHODS: The frequency of septic deaths among 38 children who received multiagent remission induction therapy, including dexamethasone (6 mg/m(2)) daily for 28 days (pilot protocol 91-01P), was compared with the frequency of septic deaths among children previously treated (protocol 87-01) and subsequently treated (protocol 91-01) in consecutive Dana-Farber Cancer Institute (DFCI) ALL trials with induction therapy that included 21 and 28 days of prednisone (40 mg/m(2)), respectively. Except for dexamethasone in protocol 91-01P, the remission induction agents used were identical in substance to those used in protocol 87-01. Protocol 91-01, the successor 91-01P, was also similar, with the exception of the deletion of a single dose of L-asparaginase. RESULTS: Sixteen of the 38 children (42%) treated on the DFCI 91-01P had documented gram positive or gram negative sepsis (17 episodes) during remission induction, including 4 toxic deaths (11%). In contrast, there were 4 induction deaths among 369 children (1%) treated on protocol 87-01 (P = 0.0035) and 1 induction death among 377 children (<1%) treated on protocol 91-01 (P = 0.0003). CONCLUSIONS: Substitution of dexamethasone for prednisone or methylprednisolone in an otherwise intensive conventional induction regimen for previously untreated children with ALL resulted in an alarmingly high incidence of septic episodes and toxic deaths. Awareness of this complication, considering that the substitution has no apparent benefit in the efficacy of remission induction, argues against its routine use in intensive induction regimens for children with ALL.

Antineoplastic Agents, Hormonal↗
PubMed2000

Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995).

The Dana-Farber Cancer Institute (DFCI) ALL consortium has been conducting clinical trials in childhood acute lymphoblastic leukemia (ALL) since 1981. The treatment backbone has included intensive, multi-agent remission induction, early intensification with weekly, high-dose asparaginase, cranial radiation for the majority of patients, frequent vincristine/ corticosteroid pulses during post-remission therapy, and for high-risk patients, doxorubicin during intensification. Between 1981 and 1995, 1,255 children with newly diagnosed ALL were evaluated on four consecutive protocols: 81-01 (1981-1985), 85-01 (1985-1987), 87-01 (1987-1991) and 91-01 (1991-1995). The 5-year event-free survival (EFS) rates (+/- standard error) for all patients by protocol were as follows: 74 +/- 3% (81-01), 78 +/- 3% (85-01), 77 +/- 2% (87-01) and 83 +/- 2% (91-01). The 5-year EFS rates ranged from 78 to 85% for patients with B-progenitor phenotype retrospectively classified as NCI standard-risk, 63-82% for NCI high-risk B-progenitor patients, and 70-79% for patients with T cell phenotype. Results of randomized studies revealed that neither high-dose methotrexate during induction (protocol 87-01) nor high-dose 6-mercaptopurine during intensification (protocol 91-01) were associated with improvement in EFS compared with standard doses. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

Adolescent↗
PubMed1999

A Phase I trial of bryostatin-1 in children with refractory solid tumors: a Pediatric Oncology Group study.

Bryostatin-1, a macrocyclic lactone, appears to elicit a wide range of biological responses including modulation of protein kinase C (PKC). PKC, one of the major elements in the signal transduction pathway, is involved in the regulation of cell growth, differentiation, gene expression, and tumor promotion. Because of the potential for a unique mechanism of interaction with tumorgenesis, a Phase I trial of bryostatin-1 was performed in children with solid tumors to: (a) establish the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD); (b) establish the pharmacokinetic profile in children; and (c) document any evidence of antitumor activity. A 1-h infusion of bryostatin-1 in a PET formulation (60% polyethylene glycol 400, 30% ethanol, and 10% Tween 80) was administered weekly for 3 weeks to 22 children (age range, 2-21 years) with malignant solid tumors refractory to conventional therapy. Doses ranged from 20 to 57 microg/m2/ dose. Pharmacokinetics were performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. Twenty-two patients on five dose levels were evaluable for toxicities. At the 57 microg/m2/dose level dose-limiting myalgia (grade 3) was observed in three patients; two of those patients also experienced photophobia or eye pain, and one experienced headache. Symptoms occurred in all patients within 24-72 h after the second dose of bryostatin-1 with resolution within 1 week of onset. Other observed toxicities (grades 1 and 2) included elevation in liver transaminases, thrombocytopenia, fever, and flu-like symptoms. The bryostatin-1 infusion was typically well tolerated. Although stable disease was noted in several patients, no complete or partial responses were observed. The recommended Phase II dose of bryostatin-1 administered as a 1-h infusion weekly for 3 of every 4 weeks to children with solid tumors is 44 microg/m2/dose. Myalgia, photophobia, or eye pain, as well as headache, were found to be dose limiting.

Adolescent↗
PubMed1997

A pilot study of continuous infusion Ara-C in combination with rhG-CSF in relapsed childhood acute myeloid leukemia.

Relapse in acute myeloid leukemia (AML) following intensive chemotherapy bears a bad prognosis. We treated 18 children with relapsed AML on two separate protocols that included continuous infusion (CI) of cytosine arabinoside (ara-C) (total dose 4gr-6gr/m2) over 96-120 hours. In an attempt to increase the fraction of blasts in S-phase and render them more sensitive to cell-cycle specific agents such as ara-C, 10 patients received 5mcg/kg rhG-CSF twice daily beginning 48 hours before and continuing through the duration of the CI ara-C (POG #9192 study). The percentage of cells is S phase before and after G-CSF administration was determined. In a second group of patients (n = 8) who received ara-C alone, endogenous concentrations of G-CSF and serial blood counts were measured (St Jude's R4 study). The rationale of the St Jude's R4 was to optimize the schedule of the second course of ara-C at a time when the patient's endogenous G-CSF concentration was increased and thus maximize the percent of cells captured in S phase. Four out of 8 patients receiving CI ara-C alone and 4 out of 10 patients receiving CI ara-C with rhG-CSF achieved a complete remission (CR) after 1 cycle of therapy. Four patients in CR underwent marrow transplantation (2 allogeneic and 2 autologous). Cell cycle analysis of blast cells cultured in vitro with or without G-CSF showed a two fold increase in the percentage of cells in S phase (P = 0.03) whereas cells obtained from patients before and after G-CSF administration showed no difference in cell cycling. Correlation between G-CSF concentrations and ANC showed a negative association indicating that the regulatory mechanisms for G-CSF production remained intact. In our relatively small series, CI ara-C achieved a CR rate of 44% with rhG-CSF having no effect on the remission rate. Although in vitro rhG-CSF increased the percentage of blasts in S phase significantly, in vivo effects were not observed. Larger studies with combinations of different hematopoietic growth factors and cell-cycle active drugs are needed to evaluate the role of these cytokines in the therapy of recurrent AML.

Acute Disease↗
PubMed1996

Role of irradiation in management of synovial sarcoma: St. Jude Children's Research Hospital experience.

The role of irradiation in the management of synovial sarcoma (SS) in pediatric patients is evaluated. The review covers all children seen at St. Jude Children's Research Hospital between May 1969 and December 1992 with the diagnosis of soft tissue sarcoma, of the 37 patients with the subtype SS, 16 received irradiation for the management of primary site disease. There were four IRS Group I, six Group II, four Group III, and two Group IV patients receiving irradiation. Tumor grade included seven Grade II, and nine Grade III lesions. TMN staging identified eight T1 and eight T2 lesions. Follow-up has ranged from 14 to 117 months (med = 33 months). All IRS Group I patients had documented local control. Five of six IRS Group II and 4/4 Group III patients have had documented local control at last follow-up. IRS Group IV patients had either local control tumor stabilization (n=1) or evidence of tumor regression (n=1) at autopsy. Complications following irradiation include wound dehiscence (n=1), surgery to revise a painful scar (n=1) extremity length discrepancy (n=2), and femoral head avascular necrosis (n=1). At last follow-up, 10 of 14 patients receiving curative intent irradiation remain alive. This review indicates questionable benefit to the addition of irradiation for patients with adequate surgical resection and having "good" tumor characteristics (Grade I, II; IRS Group I, TMN T1A,T1B. For lesions that have had incomplete resection or partial response to chemotherapy, there is evidence that irradiation may provide durable local control. The role of irradiation in those patients with IRS Group IV disease is at present confined to palliative roles until the time when more effective chemotherapy will mandate the decision to treat primary disease for curative measures.

Adolescent↗
PubMed1995

Treatment of patients with acute myelogenous leukemia: review of clinical trials of the past decade.

UNLABELLED: We discuss the history and progress of treatment for acute myelogenous leukemia (AML) in children as it has evolved over the past decade. We review the results of clinical trails for children with AML and examine the major strategies that have contributed to progresses in the treatment of this disease. Prior to the 1970's, nearly every child with AML died. Modern intensive chemotherapy, bone marrow transplantation, and advanced supportive care of critically ill patients have improved the outlook for children with this fatal disease. CONCLUSION: Although it represents only 15-20% of all childhood acute leukemias, > 30% of deaths from leukemia are still a consequence of AML, and only 30-40% of children with newly diagnosed AML are expected to achieve a long-term remission. Greater advances in treatment are expected as headway is made in understanding the complex biology of this heterogeneous disease.

Bone Marrow Transplantation↗
PubMed1994

Complete hematologic remissions induced by 2-chlorodeoxyadenosine in children with newly diagnosed acute myeloid leukemia.

The majority of children with acute myeloid leukemia (AML) who are treated exclusively with chemotherapy die of progressive disease. Improvement in outcome will likely require new active drugs capable of eradicating resistant blast cells early in the clinical course. We therefore assessed the cytoreductive potential of 2-chlorodeoxyadenosine (2-CdA), a halogenated purine analogue, in 22 consecutive children with newly diagnosed AML. The drug was administered as a single 120-hour continuous infusion (8.9 mg/m2 of body surface area per day) before the introduction of standard remission induction therapy. Six patients (27%) had complete hematologic remissions by a median of 21 days after treatment with the nucleoside (range, 14 to 33 days). Seven others had partial responses, yielding a total response rate of 59%. The drug also eliminated leukemic cells from cerebrospinal fluid in 4 of the 6 patients tested. Concentrations of 2-CdA in cerebrospinal fluid on day 5 after the initiation of treatment ranged from 12.4% to 38.0% (mean, 22.7%) of the steady-state plasma concentrations. Severe but reversible myelosuppression and thrombocytopenia developed in all patients. Analysis of factors that may have influenced the complete remission rate suggested a better outcome in patients with myeloblastic leukemia (M0-M2 subtypes in the revised French-American-British classification system). These results demonstrate clinically significant activity by 2-CdA against previously untreated AML in children, including leukemic blast cells in the central nervous system. Its use in combination chemotherapy may improve the outlook for patients with this often fatal hematologic cancer.

Adolescent↗
PubMed1994

Saturable pharmacokinetics and paclitaxel pharmacodynamics in children with solid tumors.

PURPOSE: Our aim was to evaluate the pharmacokinetics and pharmacodynamics of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in children, and to determine whether paclitaxel exhibited saturable pharmacokinetics. PATIENTS AND METHODS: We evaluated the pharmacokinetics and pharmacodynamics of paclitaxel (200 to 420 mg/m2) administered as a 24-hour intravenous (i.v.) infusion in a phase 1 study of 30 pediatric patients (age, 2.3 to 22.8 years) with refractory solid tumors. Fourteen serial blood samples were obtained during and up to 48 hours after the infusion, and paclitaxel concentrations were measured by a high-performance liquid chromatography-UV (HPLC-UV) method. Four pharmacokinetic models were compared for their ability to describe the patients' data. RESULTS: Paclitaxel disposition was not consistent with a first-order, two-compartment pharmacokinetic model. Rather, the majority of data sets were best described by a two-compartment model that incorporated both saturable tissue distribution and saturable elimination; a smaller number of patient data sets were best described by models that incorporated either saturable distribution or saturable elimination. Clearance was dose-dependent, with a median clearance at the lower dosages (< 400 mg/m2) of 161 mL/min/m2, and at the highest dosages (> 400 mg/m2) of 123 mL/min/m2 (P = .044). The duration that paclitaxel plasma concentrations exceeded 0.1 mumol/L was highly variable (range, 26 to 71 hours). There was a trend toward higher median area under the concentration-versus-time curve (AUC) in those children with musculoskeletal (72 mumol/L.h; P = .054) or neurologic toxicity (54 mumol/L.h; P = .062) versus those without toxicity (30 mumol/L.h). Toxicity was not significantly correlated with dosage. CONCLUSION: We conclude that paclitaxel distribution and elimination are saturable, and that estimates of paclitaxel systemic exposure correlate better with toxicity than does dosage.

Adolescent↗
PubMed1994

Diffuse alveolar hemorrhage associated with Mycoplasma hominis respiratory tract infection in a bone marrow transplant recipient.

An 18-year-old woman developed respiratory distress and diffuse pulmonary infiltrates after allogeneic bone marrow transplantation. Bronchoalveolar lavage findings indicated diffuse alveolar hemorrhage. Cultures of the lavage fluid and the pharynx grew Mycoplasma species; the pharyngeal isolate was identified as Mycoplasma hominis. Mycoplasma hominis infection may have an etiologic role in diffuse alveolar hemorrhage.

Adolescent↗
PubMed1994

XomaZyme-CD5 immunotoxin in conjunction with partial T cell depletion for prevention of graft rejection and graft-versus-host disease after bone marrow transplantation from matched unrelated donors.

Patients who receive bone marrow transplants from unrelated donors have a high incidence of graft-versus-host disease (GVHD). If the donor marrow is first T cell-depleted, the everity of GVHD declines but the risk of rejection rises. In an attempt to prevent both graft rejection and GVHD, we included an anti-T cell antibody-toxin conjugate (CD-5-Ricin; XomaZyme H65) in the transplant conditioning regimen. After receiving a partially T cell-depleted marrow, patients then received a second course of immunotoxin as additional GVHD prophylaxis. Eight recipients of unrelated donor marrow transplants were studied. All engrafted (ANC > 500 x 10(6)/l by day 15, range 13-20 days). One patient had grade II skin GVHD and one developed grade IV disease but the other six patients had no acute GVHD. However, there was high morbidity and mortality from virus infections associated with a sluggish return of CD4 and CD8 T cells into the normal range. Four patients died from virus disease (CMV, n = 2; EBV, n = 1; adenovirus, n = 1) and the remaining patients had frequent documented viral illnesses during the first year. We conclude that improvement in the outcome of unrelated donor marrow transplantation will require strategies which prevent rejection and GVHD coupled with attempts to accelerate immune reconstitution.

Adolescent↗
PubMed1993

Tretinoin toxicity in children with acute promyelocytic leukaemia.

Tretinoin is effective in acute promyelocytic leukaemia in adults. Data about its efficacy and safety in children are limited. We have treated 9 children with tretinoin at 45 mg/m2 per day. Pseudotumour cerebri or hyperleucocytosis occurred in 5 patients. Retinoic acid syndrome was seen in 3 cases. 1 of 2 children who developed hyperleucocytosis, pseudotumour cerebri, and retinoic acid syndrome died despite steroids and mechanical ventilation. Complete remissions with tretinoin alone were achieved in 15 patients. All 8 surviving children received consolidation chemotherapy. Our experience with tretinoin therapy suggests that toxicity is frequent in children.

Adolescent↗
PubMed1993

Parenteral nutrition associated with increased infection rate in children with cancer.

BACKGROUND: Recent meta-analyses of published controlled studies concluded that adult patients with cancer randomly assigned to receive parenteral nutrition had higher rates of infectious complications than control subjects. METHODS: The infection risk associated with parenteral nutrition was assessed in 310 pediatric patients with cancer. These patients had central venous access devices (CVAD), Hickman/Broviac (H/B) catheters, or implantable subcutaneous ports in place for the delivery of chemotherapy and supportive care. RESULTS: The median duration of CVAD placement was 363 days; a total of 450 patient years (i.e., the sum of the total years of catheters experienced from all patients studied) were examined. Overall, the infection rate was 0.06 infections/100 days. During the period of parenteral nutrition administration, the rate increased to 0.5 infections/100 days. Among patients who received parenteral nutrition, there were no significant differences in any clinical parameter between the patients who developed an infection and those who did not. When evaluating the entire study population, infection was more likely to occur in patients who had acute nonlymphocytic leukemia (P < 0.01) or H/B catheters (P < 0.01), or who received parenteral nutrition (P < 0.02); there was no relationship between infection and catheter duration, days hospitalized, or days neutropenic (absolute neutrophil count < 0.5 x 10(9)/l). Only CVAD type and parenteral nutrition retained significance in a multivariate Cox proportional hazards model. After adjustment for diagnosis and CVAD type, the risk of infection was 2.4-fold greater in patients given parenteral nutrition (95% confidence interval 1.5 to 3.9; P < 0.001). CONCLUSION: These data confirm that administration of parenteral nutrition is associated with an increased risk of infection in children who have CVAD in place for cancer therapy.

Adolescent↗
PubMed1993

Adverse prognostic features in 251 children treated for acute myeloid leukemia.

Potential predictors of event-free survival (EFS) were assessed in 251 consecutively diagnosed children treated for acute myeloid leukemia (AML) on three successive clinical trials. The lack of significant differences in 4-year EFS for these studies (20% +/- 4%, 29% +/- 4%, and 20% +/- 7%) permitted combined analysis of presenting features. Splenomegaly (P = .002), coagulation abnormalities (P = .001), leukocyte count > or = 10 x 10(9)/L (P = .002), and age > 14 years (P = .01) were statistically significant predictors of a poorer EFS by univariate analysis and retained significance in multivariate analysis. Age < 2 years and monocytic leukemias (often cited as adverse factors in AML) showed no prognostic influence in this study. The estimated relative risk of failure for a child with a single adverse feature at diagnosis was at least 1.4 times greater than that for a patient with no adverse features. For children with two or more adverse features, the relative risk increased by more than threefold. These clinical variables, alone or in combination, may identify important subgroups of patients with AML at high risk for failure and for whom improved or alternative therapies are especially important.

Acute Disease↗
PubMed1993

Phase I trial of paclitaxel in children with refractory solid tumors: a Pediatric Oncology Group Study.

PURPOSE: A phase I study was performed to describe the principal toxicities and identify the maximum-tolerated dose (MTD) of Taxol (paclitaxel; Bristol-Myers Squibb Co, Wallingford, CT) in children with therapy-resistant solid tumors. Additionally, the pharmacokinetic disposition of Taxol in children was studied, and preliminary evidence of the activity of Taxol against pediatric solid tumors was assessed. PATIENTS AND METHODS: Twenty-four-hour continuous infusions of Taxol were administered every 21 days to children (median age, 12 years; range, 2 to 22) with refractory solid tumors. Doses ranged from 200 to 420 mg/m2, there was no intrapatient dose escalation. RESULTS: A total of 62 courses of Taxol were administered to 31 patients. Two patients developed acute anaphylaxis during their second infusion of taxol at doses of 200 mg/m2 and 350 mg/m2, respectively. No other allergic reactions were documented. Myelosuppression occurred at all dose levels, but was of short duration (< or = 7 days) and did not appear to increase with consecutive courses or at higher dosage levels. A stocking-and-glove peripheral neuropathy became evident at doses > or = 290 mg/m2. Dose-limiting neurotoxicity occurred at 420 mg/m2 and comprised a significant fine-motor and peripheral neuropathy in one patient, and a tonic-clonic seizure in another. End-of-infusion plasma concentrations ranged from 0.40 to 6.4 mumol/L, and were not found to be dose-dependent over the range of doses studied. A complete response was documented in one patient, partial response in two, and minimal response in one for an overall response rate of 13%. CONCLUSION: Neurotoxicity was dose-limiting when Taxol was administered by 24-hour continuous infusion to pediatric patients with relapsed solid tumors. In this population, the recommended dose for phase II trials is 350 mg/m2/d.

Adolescent↗
PubMed1993

Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation.

PURPOSE: Patient records were reviewed to identify cases of secondary acute myeloid leukemia (AML) with clinical and cytogenetic features characteristic of classic epipodophyllotoxin-related AML in patients whose prior treatment for cancer did not include these agents. PATIENTS AND METHODS: Four cases of secondary AML with chromosomal abnormalities involving bands 11q23 and 21q22, in the absence of prior treatment with etoposide or teniposide, were identified among patients treated at St Jude Children's Research Hospital between January 1980 and April 1992. RESULTS: The four identified patients were initially treated for rhabdomyosarcoma, non-Hodgkin's lymphoma (n = 2), and Hodgkins' disease. Prior chemotherapy included relatively low cumulative doses of doxorubicin (median, 150 mg/m2; range, 120 to 375 mg/m2) and cyclophosphamide (median, 3,100 mg/m2; range, 2,250 to 11,400 mg/m2). All four patients had received radiation therapy: 59.4 Gy to the right middle ear for rhabdomyosarcoma; 15 Gy and 12 Gy to the abdomen and right lower quadrant, respectively, for non-Hodgkin's lymphoma; 27 Gy to the right orbit for non-Hodgkin's lymphoma; and 36.6 Gy to the mantle-paraaortic-spleen regions plus 20.4 Gy inverted-Y radiation at relapse for Hodgkin's disease. Secondary AML was diagnosed a median of 38 months after initial diagnosis (range, 14 to 55). Leukemic cell translocations involved band 11q23 in two cases and band 21q22 in two. Although all patients obtained a complete remission (CR), only one remains disease-free (at 34 months), following an allogeneic bone marrow transplant. CONCLUSION: Intercalating topoisomerase II inhibitors (doxorubicin, dactinomycin), when combined with alkylating agents and irradiation, may cause secondary AML.

Acute Disease↗