Acute lymphoblastic leukemia in adults

Opinion statement The therapy of acute lymphoblastic leukemia (ALL) in adults has built on the remarkable success achieved in the treatment of this disease in children. However, older age and other adverse risk factors seen more commonly in adults than in children have lessened the success of the treatment of ALL in comparison with what has been achieved in children. The treatment of ALL depends on the use of intensive multi-agent chemotherapy given over 6 to 9 months in combination with central nervous system prophylactic therapy with cranial radiation and intrathecal chemotherapy followed by maintenance chemotherapy for 2 to 3 years. This therapy has allowed younger patients with newly diagnosed ALL to achieve complete remission in 80% to 90% of cases, but has still resulted in subsequent relapse in most patients. For high-risk patients with ALL, allogeneic blood and marrow transplant (BMT) from a related or unrelated donor can improve the outcome compared with chemotherapy. The role of autologous transplantation in ALL remains uncertain, as does the role of allogeneic transplant in standard-risk patients. This issue continues to be the subject of large, randomized trials. New agents and improvements in supportive care bring the hope that more patients with ALL will be cured in the future.     

Acute lymphoblastic leukemia in infants less than one year of age: a cumulative experience of the Children's Cancer Study Group

A retrospective review of all 115 infants less than 1 year of age with acute lymphoblastic leukemia (ALL) entered on a consecutive series of recent Children's Cancer Study Group (CCSG) leukemia protocols was undertaken to examine in detail the outcome and clinical course of a large group of similarly treated infants. In comparison to the 4,392 children older than 1 year, entered on the same studies, infants had a significantly (P = .0001) increased incidence of leukocytosis, hepatosplenomegaly, meningeal leukemia at presentation, hypogammaglobulinemia, and failure to achieve complete remission (CR) status by day 14 of induction therapy. In contrast, lymphadenopathy, non-L1 French-American-British (FAB) morphology, mediastinal mass, and T cell leukemia were not more frequently observed. Ninety percent of these infants successfully completed the induction phase of therapy. With a median follow-up of 35 months, life table estimate of disease-free survival is only 23% at 4 years. Identical disease-free survival rates for infants were observed in each of the individual studies reviewed. Excessive toxicity resulting in limitation of therapy delivered was not a causative factor for the disappointing outcome of these patients. Rather, early disease recurrence, characterized by bone marrow relapse (55%) and CNS (22%) relapse, was the major factor responsible for the extremely poor prognosis of this patient group. Identical CNS relapse rates were observed in those patients who received cranial irradiation as part of CNS prophylaxis (21.8%) and in those patients who did not receive cranial radiotherapy (24%). Results of salvage therapy for patients who experienced systemic or extramedullary relapse were dismal. Debilitating neuropsychologic sequellae, presumably related to CNS irradiation, have been observed in 50% of the small number of long-term survivors. Infants less than 1 year of age with ALL present with a constellation of features which predict a poor outcome and constitute the group of children with ALL at greatest risk for treatment failure.     

Cranial nerve palsy in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma

Forty-five children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma had cranial nerve palsy (CNP) as a complication of their disease. Twenty-two of these children had CNP initially and 23, at relapse, with or without previous hematologic relapse. Only one of the 23 patients with CNP at relapse was a long-term survivor. In contrast, 11 of the 22 children who had CNP initially survived in remission for 3+ months to 13+ years. Two factors are associated with an improved outcome for patients with CNP at diagnosis: treatment after 1979 (P less than 0.004) and male gender (P less than 0.01). Patients who received radiation therapy fared better than those for whom radiation was not given (disease-free survival at 2 years 53% versus 29%). The authors conclude that CNP signifies an aggressive or advanced disease requiring intensive systemic chemotherapy and that the role of irradiation should be examined for this group of patients.     

Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: a pediatric oncology group study .

PURPOSE: Isolated meningeal relapse in children with acute lymphoblastic leukemia (ALL) usually has been followed by bone marrow relapse and limited survival. The purpose of this study was to prevent marrow relapse by administering intensive therapy before delayed craniospinal radiation. PATIENTS AND METHODS: Eighty-three patients with ALL in first bone marrow remission with an isolated CNS relapse were treated with systemic chemotherapy known to enter into the CSF and intrathecal chemotherapy for 6 months. Craniospinal irradiation (24 Gy cranial/15 Gy spinal) was then administered, followed by 1.5 years of maintenance chemotherapy. RESULTS: All 83 patients achieved a second remission. The 4-year event-free survival (EFS) rate was 71.1% +/- 5.3%. There was a fourfold increased risk of relapse for children whose initial remission was less than 18 months. The 4-year EFS rate for patients with a first complete remission >/= 18 months was 83.3% +/- 5.3%, and for those with a first complete remission less than 18 months, it was 46.2% +/- 10.2% (P =.0002.) There was a low incidence of neurologic toxicity and an unexpectedly high rate of allergic reactions to L-asparaginase. Five patients developed secondary malignancies: two with acute nonlymphoblastic leukemia during therapy, one with myelodysplasia after therapy, and two with brain tumors 1.5 to 2 years after cessation of therapy. CONCLUSION: For children with ALL and an isolated CNS relapse, treatment that delays definitive craniospinal irradiation by 6 months to allow for more intensive systemic and intrathecal chemotherapy results in better EFS than has been previously reported. Using this approach, the long-term prognosis for children with first complete remission >/= 18 months is comparable to that at the time of original diagnosis of ALL.     

Treatment of acute myelogenous leukemia in children

Progress in the treatment of childhood AML has not equalled the advances obtained in the management of ALL. Two recent chemotherapy studies (i.e. VAPA and BFM 78), however, reported marked increase in the proportion of long-term remissions. The initial therapy of the cooperative study BFM 78 consisted of two 4-week phases of intensive induction/consolidation with 7 different drugs and cranial irradiation followed by maintenance with thioguanine and cytosine arabinoside for 2 years and additional adriamycin during the first year. A total of 151 children with AML were enrolled in the study from 30 centers. Of these 119 (79%) patients achieved complete remission. After a median observation time of 34 (14-57) months, there have been 46 relapses. CNS was involved in 6 of these relapses. Life table analyses revealed the following probabilities after 4 1/2 years: survival: 46%; disease-free survival: 41% (total group), 52% (remission group); disease-free interval 56% (remission group). The risk of relapse appears to decrease considerably after 2 1/2 years. No risk factors for the occurrence of relapse have been identified.     

Autologous peripheral blood stem cell transplantation for adults with B-lineage acute lymphoblastic leukemia: a pilot study

We conducted a pilot study on autologous peripheral blood stem cell transplantation (PBSCT) for 11 adults with B-lineage acute lymphoblastic leukemia (ALL) in first complete remission (CR) or even in those with more advanced stages. All patients achieved CR by induction therapy, of whom 10 were treated with anthracycline, vincristine and prednisolone-based regimens. After consolidation therapy, all patients except one received high-dose cytarabine followed by granulocyte colony-stimulating factor (G-CSF) administration to collect PBSCs. Ten patients received busulfan 4 mg/kg for 4 days, etoposide 20 mg/kg for 3 days and ranimustine 200 mg/m2 for 2 days as a conditioning regimen. One received a regimen consisting of etoposide, cyclophosphamide and total body irradiation. From day 1, G-CSF was given intravenously, and no additional chemotherapy was administered. At the median follow-up time of 30.8 months, four of six patients with standard-risk B-lineage ALL survived within the range of 19.7 to 85.4 months without relapse. In contrast, only one of five with high-risk B-lineage ALL survived for 36.3 months without relapse. Autologous PBSCT as post-remission therapy may prolong CR in adults with standard-risk B-lineage ALL.     

Current management and challenges of malignant disease in the CNS in paediatric leukaemia

With 5-year event-free survival of 80% now commonplace for paediatric acute lymphoblastic leukaemia (ALL), and 50% for paediatric acute myeloid leukaemia (AML), recent efforts have focused on optimum risk-directed treatment. Because cranial irradiation can cause many acute and late complications (eg, second cancers, neurocognitive deficits, endocrine disorders, and growth impairment), it has been largely replaced by intensive intrathecal treatment and systemic chemotherapy. Prophylactic cranial irradiation (12-18 Gy) is given to 2-20% of patients with ALL who have an increased risk of CNS relapse (such as T-cell immunophenotype, overt CNS disease, high-risk cytogenetic features, or poor response to remission induction treatment), and for the estimated 2% of patients with AML who have overt CNS disease at diagnosis. Although this strategy restricts CNS relapse to 3-8% of patients, several challenges remain. Methods need to eliminate relapse without the use of cranial irradiation in very high-risk patients. Effective retrieval treatment is needed for patients with relapsed or refractory CNS leukaemia, and intrathecal treatment with improved efficacy and reduced side-effects remains a long-term objective. Perhaps the most formidable challenge is to treat children with CNS relapse after a short initial remission or cranial irradiation.     

Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: Outcomes of late effects on pituitary function and growth in long‐term survivors

It is well known that prophylactic cranial irradiation is highly effective in preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL). Nevertheless, there have been very few reports on the late effects, especially pituitary function and growth, in long‐term survivors who were treated with 18 Gy cranial irradiation in childhood. The subjects consisted of 35 children with ALL who were treated with prophylactic 18 Gy cranial irradiation at Kanagawa Children's Medical Center between October 1981 and February 1995. All patients received cranial irradiation after first attaining complete remission with induction chemotherapy, according to the treatment protocols prescribed by the Tokyo Children's Leukemia Study Group (TCLSG) and Tokyo Children's Cancer Study Group (TCCSG). Their ages at the time of cranial irradiation ranged from 2.2–15.0 years (mean 6.8). We evaluated their pituitary functions by measuring their pituitary hormone values 0.7–11.3 years (mean 6.0) after cranial irradiation and their growth by analyzing their height standard deviation score (SDS) at diagnosis of ALL and their final height SDS at the mean follow‐up period of 8.2 years after cranial irradiation. Height SDS is defined as the difference between the patient's height and the mean height of their age and sex, divided by the standard deviation of their age and sex. Eight of 35 patients had ALL relapse, involving the bone marrow in seven patients and the CNS in only one. Six of the eight patients with relapse died 1.5–6.6 years after cranial irradiation and the other two patients were salvaged by further intensive therapies. The remaining 27 relapse‐free patients have survived for 1.4–15.8 years (mean 10.1) after cranial irradiation. Twenty‐six of the 29 survivors are long‐term survivors of more than 5 years. Although there was one patient with an abnormal result in each value of growth hormone (GH), adrenocorticotropic hormone (ACTH), and prolactin (PRL), and two patients with abnormal results in thyroid‐stimulating hormone (TSH) values, none of the patients had clinical symptoms of pituitary hormone abnormality and none required hormone supplements. The final height SDS decreased significantly compared with the height SDS at diagnosis of ALL in the long‐term survivors (P = 0.001) and the height SDS of the patients who had received cranial irradiation at a young age tended to decrease gradually (P = 0.019). However, no patient showed severe growth failure. It is considered that prophylactic 18 Gy cranial irradiation plus chemotherapy for ALL in childhood can effectively prevent CNS relapse and is unlikely to produce clinically significant late effects, although it may cause slight pituitary hormone abnormality. © 2002 Wiley‐Liss, Inc.     

Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.     

The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia

We assessed the influence of an initial isolated meningeal relapse on treatment outcome in 839 children with acute lymphoblastic leukemia (ALL) who were admitted to St Jude Children's Research Hospital (Memphis) from mid-1967 through mid-1979. The patients were entered in a series of five clinical trials (Total Therapy Studies V through IX), each designed to test one or more modifications of treatment for ALL. Two groups were compared: 699 children who received CNS prophylaxis (2,400-rad craniospinal irradiation or 2,400-rad cranial irradiation plus intrathecal methotrexate) v 56 who did not. Our results, obtained with a time-dependent covariate model and a matching technique, indicate a 2 to 3.5-fold increase in the risk of hematologic relapse or death among patients who experienced an isolated CNS relapse compared with similar patients (matched for leukocyte count and length of complete remission) who remained free of CNS involvement. Of the 107 children with an initial isolated CNS relapse, 89 (83%) have died or have had a subsequent relapse. There was no detectable difference in the rate of hematologic relapse or death after a CNS relapse between patients who had received preventive therapy and those who had not. We conclude that CNS prophylaxis is important both for the prevention of initial CNS leukemia and for reducing the risk of hematologic relapse or death subsequent to a CNS relapse.     

Impact of three methods of treatment intensification on acute lymphoblastic leukemia in children: long-term results of St Jude total therapy study X.

Long-term follow-up observations are reported on 427 patients who received one of three different intensified therapies in total therapy study X for acute lymphoblastic leukemia (ALL). In the trial for 'standard-risk' ALL, 154 of 309 patients in complete remission were randomized to receive high-dose methotrexate (HDMTX, 1 g/m2) periodically during the first 72 of 120 weeks of standard continuation therapy with 6-mercaptopurine and oral MTX; the remaining 155 patients received 1800 cGy cranial irradiation and intrathecal MTX, followed by 6-mercaptopurine/MTX therapy interrupted from week 36-71 for substitution of two other pairs of drugs. At 9 years of follow-up, significantly higher proportions of patients in the HDMTX group have maintained complete remissions (64 +/- 7%, SE, vs. 52 +/- 6%, p = 0.03), hematologic remissions (73 +/- 6% vs. 62 +/- 6%, p = 0.03), and testicular remissions (94 +/- 5% vs. 80 +/- 8%, p = 0.03); however, the proportion continuing in central nervous system remission has been lower (84 +/- 5% vs 93 +/- 4%, p = 0.02). In the evaluation of teniposide/cytarabine and delayed cranial irradiation for 'high-risk' ALL, 36 +/- 9% of 101 patients are predicted to be event-free survivors at 9 years. Altogether, 217 (51%) of the 427 patients are event-free survivors after at least 7 years of follow-up (median, 9 years); an additional 75 patients are alive and free of leukemia for a median of 6.4 years after successful remission retrieval therapy, boosting the total number of long-term survivors to 292 (68%). These results establish the efficacy of HDMTX for patients with standard-risk ALL and indicate the potential of teniposide/cytarabine for use in multiagent regimens for patients with high-risk disease. The overall survival figure, 68%, affords a benchmark for other studies assessing long-term outcome in ALL.     

Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group

On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX.     

Long survival in childhood lymphoblastic leukaemia

Long term follow-up of 378 children with acute lymphoblastic leukaemia (ALL) treated at a single centre showed that at six years from diagnosis 202 (53%) were alive, of whom 140 (37%) remained in first remission. Only three children had a first relapse after six years. Children who survived six years despite a single extramedullary relapse in the testis or CNS were likely to remain in second remission but patients with previous marrow or with multiple relapses continued at risk for up to ten years from diagnosis. Presenting factors influencing event-free survival were: leucocyte count, age and sex. After allowing for these factors morphological (FAB) subtype and liver enlargement retained their prognostic significance. Immunological type of ALL was not of independent prognostic significance, except for the small number of patients with B-ALL. Most factors lost their significance after 2-4 years. It is concluded that patients alive 6 years from diagnosis without relapse or even with a single extramedullary relapse of ALL, have a high chance of prolonged survival and cure.     

Improved survival in adult acute lymphoblastic leukemia. Need for more effective CNS prophylaxis

Using a multimodality approach to adult acute lymphoblastic leukemia, 93% of patients achieved a complete remission; among patients achieving a complete remission, 43% are predicted to remain disease-free for 5 years. Despite use of cranial irradiation (2400 rad) and intrathecal methotrexate (12 mg X 5), CNS relapse occurred in 5/14 patients (36%). With improved systemic therapy of adult ALL, survival is increased and "standard" CNS prophylaxis is not as effective as it appeared to be when systemic remissions were of shorter duration. More effective approaches to CNS prophylaxis need to be devised.     

Comparison of maintenance treatment regimens for first central nervous system relapse in children with acute lymphocytic leukemia. A Pediatric Oncology Group study

Eighty-seven children with central nervous system (CNS) leukemia were randomized to receive either induction intrathecal chemotherapy (ITC) and cranial irradiation (CRT) plus maintenance ITC, or induction ITC and craniospinal irradiation (CSpRT) with no maintenance ITC. ITC consisted of six weekly injections of methotrexate, hydrocortisone, and arabinosylcytosine. Also, intensification of systemic induction and maintenance chemotherapy was given. CRT + ITC was given as CRT, 2400 rad in 12 fractions followed by ITC maintenance bimonthly for 2 years. Craniospinal irradiation consisted of CRT + 1400 rad in ten fractions to the spine. Randomization was stratified according to whether CNS leukemia occurred at initial diagnosis of acute lymphocytic leukemia (ALL) (Stratum I, 15 patients), during first bone marrow (BM) remission (Stratum II, 49 patients), simultaneous with first BM relapse (Stratum III, 12 patients), or during second BM remission (Stratum IV, 11 patients). The median follow-up for patients who remain at risk is 15 + months. Eight children (seven on CRT + ITC, one on CSpRT) developed presumed therapy related encephalopathy. In Stratum II, 16 of 29 (55%) patients receiving CRT + ITC experienced adverse events: 3 deaths during continuous complete remission (CCR) and 13 relapses (2 CNS, 1 CNS + BM, 1 BM + testes, and 2 testes) as compared with only 5 relapses in 20 (25%) patients on CSpRT (1 CNS, 1 CNS + BM, 1 BM, and 2 testes). The children on both regimens were comparable for sex, race, age at initial ALL diagnosis, time from ALL diagnosis to first episode of CNS leukemia, systemic therapy both before and after CNS relapse, and number of blasts in the spinal fluid at diagnosis of CNS leukemia. The conclusion is that children with isolated CNS leukemia can achieve prolonged survival with aggressive therapy, and that CSpRT is possibly less toxic and more likely than is CRT + ITC to prevent subsequent BM and testicular relapse (P less than 0.02), but not subsequent CNS relapse (P = 0.7). A possible systemic therapy effect of spinal irradiation is postulated to explain the superiority of CSpRT.     

The relationship of sex and treatment modality to neuropsychologic outcome in childhood acute lymphoblastic leukemia.

PURPOSE: Long-term adverse neurobehavioral sequelae frequently are observed in pediatric patients treated for acute lymphoblastic leukemia (ALL). To clarify the relative contribution of cranial irradiation (CRT) therapy and drug therapy to these outcomes, we evaluated neuropsychologic outcomes associated with different doses of CRT and intravenous (IV) methotrexate (MTX) in long-term survivors. PATIENTS AND METHODS: Fifty-one patients treated for ALL on Dana-Farber Cancer Institute protocol 81-01 were evaluated by standardized cognitive and academic achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received 1,800 cGy or 2,800 cGy CRT, respectively. A subgroup of these patients was randomized to receive MTX during remission induction, either as a single low dose (LD; 40 mg/m2) or a single high dose (HD; 4 g/m2) with leucovorin rescue. RESULTS: Sex and MTX randomization jointly predicted the intelligence quotient (IQ). Fifty percent of girls versus 14% of boys exhibited low IQ (less than 90; P = .01); 80% of girls who received HD MTX versus 25% of girls who received LD MTX exhibited low IQ (P = .03). In contrast, risk group better predicted performance on tasks sensitive to verbal memory and/or coding. CONCLUSIONS: We conclude that (1) significant neurotoxicity occurred principally in girls; (2) increased dose intensity of IV MTX was associated with lower IQ, but only in girls; and (3) increased dose of CRT may have been associated with impairment of verbal memory and coding.     

Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) accounts for 25% of childhood cancer. Clinical and biological parameters define prognostic categories and therapeutic approaches. For the majority of children with B-progenitor ALL, age (1-9 yrs) and white blood count (WBC<50,000) indicate standard risk disease; WBC>50,000 and age>9 yrs. define eligibility for high-risk protocols. Infants (<1 yr. old) are high-risk, frequently associated with chromosomal t(4;11) translocation and extramedullary disease. T-cell immunophenotype is usually associated with clinical high-risk features, including older age, high WBC, and extramedullary disease. T-cell immunophenotype is usually associated with clinical high-risk features, including older age, high WBC, and extramedullary disease. Current regimens include induction chemotherapy, consolidation (often including high-dose systemic methotrexate, MTX), and continuation phases; intensification or reinduction is incorporated for high-risk disease. Preventive CNS therapy is a critical component of therapy. Intrathecal (IT) chemotherapy (MTX +/- cytosine-arabinoside and hydrocortisone) and systemic agents provide adequate CNS therapy in standard risk patients. The "threshold" for using preventive cranial irradiation (Crl, 18 Gy) varies among protocols, but systematically includes those with T-cell ALL and WBS>50,000; other criteria may include B-progenitor ALL with WBC>100,000,philadelphia chromosome positive ALL, residual marrow disease at day 7, or male gender, For the 5% of children with CNS leukemia at diagnosis (defined as CSF with 5 or greater WBC/uL and positive cytology), Crl is administered at does of 18 to 24 Gy. Recent series show a CNS relapse rate approximating 5% Reinduction chemotherapy, IT therapy, and subsequent craniospinal irradiation ( typically 24, Gy Crl, 15 Gy spine) achieve durable secondary disease control in greater than 60% of cases with isolated CNS relapse. High-dose systemic MTX has virtually eliminated testicular relapse. CNS toxicities (including leukoencephalopathy) relate to systemic and IT MTX as well as Crl. Late neuropsychologicral data following Crl at 18 Gy show little intellectual deficit compared with children receiving MTX- based preventive therapy alone. Neuroendocrine dysfunction is apparent in long-term survivors following Crl at 24 Gy. The relative efficacy and toxicities of Crl versus more intensive MTX-based regimens are yet controversial. Overall disease-free survival in ALL approximates 70% in contemporary series.     

Soft-tissue sarcomas of the head and neck in children

Thirty-two children aged three months to 17 years (median six years) were diagnosed with soft-tissue sarcoma of the head and neck and treated at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania from 1971 to 1981. Thirty-one received chemotherapy and all received radiation therapy (RT). Twenty-five patients had pre-treatment computed tomography (CT) scans, which were used for staging and treatment planning. Doses of radiation therapy ranged from 3000 to 7300 rad to the primary tumor (median 5000 rad). The overall five-year survival of the entire group of 32 patients was 75%. Ten of the 32 patients had invasive cranial parameningeal disease as demonstrated by bony erosion at the skull base, seen on CT in eight and plain radiographs in two patients. Eight of these 10 patients have developed recurrent sarcoma: four in the meninges, two locally, one regionally and one distantly. Five of these 10 children with invasive cranial parameningeal sarcoma received 3000 rad of prophylactic cranial irradiation, begun within the first 12 days of chemotherapy, and none developed meningeal disease. In contrast, only one of the 22 patients without invasive cranial parameningeal disease has relapsed (local recurrence). The data suggest that soft-tissue sarcomas of the head and neck in children without invasion into the base of the skull (invasive cranial parameningeal disease) are usually cured. CT scans are essential for staging. Patients with invasion of the base of the skull may be protected from meningeal relapse by early cranial irradiation, although they still are at high risk for relapse in other sites.     

Ocular relapse in the anterior chamber in childhood acute lymphoblastic leukemia

We reviewed 11 cases of ocular relapse in the anterior chamber in children with acute lymphoblastic leukemia (ALL), representing 0.5% of all primary relapses seen at this center. Nine patients had hypopyon, and two had iris involvement only. Concomitant testicular relapse was present in two children and hematologic relapse in one. Ocular relapse occurred at 12 to 74 months (median, 36 months) from the data of initial diagnosis. Children who relapsed after therapy was discontinued did so within 1 year of completing therapy. Topical steroids and systemic chemotherapy were administered to all patients with ocular relapse; four also received radiation to the involved eye (600 to 1,050 cGy). Four children, each with a prolonged initial complete remission, remain free of disease for 15+, 32+, 34+, and 145+ months following anterior chamber relapse; three had received radiation therapy. Five patients died of recurrent leukemia, and two of infection while in remission. Aggressive retreatment appears warranted in cases of anterior chamber relapse of ALL, as some of these children may attain prolonged new remissions.     

Behavioral and educational limitations after chemotherapy for childhood acute lymphoblastic leukemia or Wilms tumor

BACKGROUND: The improved prognosis of childhood cancer makes monitoring of functional outcome important. The purpose of this study was to evaluate behavioral and educational functioning in survivors of childhood acute lymphoblastic leukemia (ALL) or a Wilms tumor. In this study, children with ALL received central nervous system directed chemotherapy without cranial irradiation. METHODS: In a multicenter study, behavioral functioning and school performance was examined in 199 children age 4 to 18. Sixty-four children were at least 1 year from finishing treatment with chemotherapy for ALL (n = 28) or a Wilms tumor (n = 36). They were compared with siblings (n = 37) and with a control group of healthy schoolchildren (n = 98). RESULTS: A moderately increased risk of behavioral and educational problems was found in children with ALL but not in children with Wilms tumor. School performance was poorer in children with ALL attending primary school compared with same-age peers; however, the rate of utilization of special education services was low. Teacher-rated behavior and mathematics performance was correlated with attention function in children with ALL. An excess of problem behavior and underperformance at school was found in the ALL high-risk group compared with the standard-risk group. No differences were found between siblings and controls. CONCLUSION: Evidence is provided of subtle but significant behavioral and educational problems in survivors of childhood ALL, but no dysfunctions in survivors of a Wilms tumor. Careful follow-up of children with ALL treated with chemotherapy only is warranted.