Malnutrition is an adverse prognostic factor in the response to treatment and survival of patients with acute lymphoblastic leukemia at the usual risk

A group of 43 pediatric patients with standard risk acute lymphoblastic leukemia (ALL) was studied prospectively and treated with a protocol that included adriamycin, vincristine and prednisone (HOP) to induce remission; cranial irradiation and intrathecal methotrexate (MTX) as CNS prophylaxis and mercaptopurine and MTX together with pulses of HOP every three months to maintain remission. Complete remission (CR) was achieved in 95.3% of the group; 5-year survival was 67%. The following variables were analyzed in the outcome to treatment: Age, sex, WBC at diagnosis, FAB morphology, CALLA/CD10 reactivity of the blast cells, lymph node, liver or spleen enlargement, site of treatment (private practice versus city hospital) and malnutrition. None of these variables had a significant impact in survival, but malnutrition. Under-nourished children (UNC) n = 16, had a significant worse outcome than well-nourished children (WNC) n = 27. Although CR was achieved in 98% of WNC versus 94% of UNC, five-year survival was 83% for WNC and 26% for UNC (p less than .001); relapses were observed in 18% of WNC and 75% of UNC (p less than .0005). Relapses presented more frequently in the bone marrow in UNC than in WNC (56% versus 7% p less than .0001). The doses of maintenance chemotherapy had to be reduced in 68% of UNC and 10% of WNC (p less than .005). The poor outcome to treatment observed in UNC was due to systemic relapses, apparently related to a poor tolerance to maintenance chemotherapy. Malnutrition might be included as an adverse prognostic factor in the outcome to treatment of children with ALL, in developing countries.     

Allogeneic bone marrow transplantation in first remission for children with ultra-high-risk features of acute lymphoblastic leukemia: A children's oncology group study report.

The prognosis for childhood acute lymphoblastic leukemia (ALL) has improved dramatically over the past quarter of a century. Despite improvements in the treatment of childhood ALL, relapse still occurs in 20%-30% of patients. Although many of these relapses occur in the "standard-risk" patients, approximately 10% of these patients present at diagnosis with clinical and biological features that identify them as having a very high risk of relapse. Children (2 months to 21 years) with > or =1 ultra-high-risk feature (UHRF) of ALL in first remission treated on a frontline Children's Cancer Group (CCG) ALL study with a matched family allogeneic donor were eligible for study entry onto CCG-1921 and an allogeneic bone marrow transplant (AlloBMT). Each patient received fractionated total body irradiation (1200 cGy) and cyclophosphamide (120 mg/kg) conditioning therapy followed by unmobilized BM from a matched family donor. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and cyclosporin. Twenty-nine patients with a median age of 8.7 years with UHRF ALL in first complete remission (CR1) received an AlloBMT from a family member. The incidence of grade II-IV acute GVHD was 20.7% and the incidence of chronic GVHD was 3.7%. AlloBMT conditioning regimen was well tolerated and only 1 patient (3%) had treatment-related mortality. Ten patients (35%) died due to progressive disease. The 5-year event-free survival (EFS) for all patients was 58.6% and patients without cytogenetic abnormalities had a 5-year EFS of 77.8%. The 5-year EFS rates for infants and non-infants were 20.0% and 66.7% (log-rank test, P = .01), respectively. Patients with Philadelphia chromosome-positive ALL had a 5-year EFS of 66.7%. The children with UHRF of ALL may benefit from AlloBMT in CR1, especially patients with primary induction failure and Philadelphia chromosome-positive ALL. Randomized prospective cooperative group studies are required to establish the role of allogeneic hematopoietic stem cell transplantation versus intensive chemotherapy in children with UHRF ALL in CR1.     

Cognitive status of children treated with central nervous system prophylactic chemotherapy for acute lymphocytic leukemia.

Treatment-related cognitive impairments have been reported for survivors of childhood leukemia following prophylactic central nervous system (CNS) treatment with craniospinal radiation. We examined the neurocognitive status of 46 children with acute lymphocytic leukemia (ALL) to assess the impact of a regimen consisting of systemic chemotherapy and prophylactic CNS chemotherapy. By comparing three groups of ALL children (i.e., patients whose diagnosis was recent, patients 1 year postdiagnosis currently receiving CNS prophylactic chemotherapy, and off-therapy patients who had been treated with chemotherapy for 3 years) and their healthy siblings on measures of sequential and simultaneous processing, we were able to examine the effects of CNS prophylactic and systemic chemotherapy at various points during treatment. Results indicate that the children who had received a 3-year course of chemotherapy (off-therapy patients) were more impaired on tasks involving right-hemisphere simultaneous processing than were sibling controls or ALL children whose diagnosis was recent and whose treatment had just begun. Age at diagnosis did not interact with the effects of chemotherapy. These findings support the need for continued evaluation of cognitive functioning in ALL, children receiving CNS prophylactic chemotherapy to identify potential harmful neurocognitive sequelae of treatment.     

Augmenting Total Body Irradiation with a Cranial Boost before Stem Cell Transplantation Protects Against Post-Transplant Central Nervous System Relapse in Acute Lymphoblastic Leukemia

The purpose of this study was to determine the effect of a pretransplant cranial boost (CB) on post-transplant central nervous system (CNS) relapse and survival in acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) using a total body irradiation (TBI)-containing preparation regimen. Two hundred thirteen ALL patients were treated consecutively at our institution with allogeneic HSCT. Conditioning included TBI (1320?cGy in 8 fractions given twice daily) and cyclophosphamide (120?mg/kg) with or without fludarabine (75?mg/m²). Patients were divided into 4 groups based on history of CNS disease and whether a CB was given. Of the 160 patients with no history of CNS disease, none received a CB (CNS?/CB?). Of the 53 patients with prior CNS disease, 41 had not received prior cranial irradiation. Thirty of these 41 received a CB of 900 to 1000?cGy in 5 daily fractions (CNS+/CB+), whereas the other 11 did not receive a CB because of physician preference (CNS+/CB?). The remaining 12 patients with prior CNS involvement had previously received cranial irradiation and thus were not candidates for a CB (CNS?+?PriorRT). Two-year CNS relapse risk, overall survival (OS), and disease-free survival (DFS) were calculated using Kaplan-Meier analysis. Seven patients experienced post-transplant CNS relapse: 4 in the CNS?/CB? group, 2 in the CNS+/CB? group, and 1 in the CNS?+?PriorRT group. None of the 30 patients who received a CB relapsed in the CNS. Two-year CNS relapse risk was 0% in the CNS+/CB+ group compared with 21% (95% CI, 0% to 45%) in the CNS+/CB? group (P?=?.03). Two-year OS and DFS did not differ between the groups. In conclusion, among ALL patients with prior CNS leukemia, there was a trend toward a reduced risk of post-transplant CNS relapse in patients who received a CB. However, the addition of a CB did not appear to have an impact on OS or DFS.     

Neuropsychological sequelae of central nervous system prophylaxis in survivors of childhood acute lymphoblastic leukemia

We assessed neuropsychologically 106 children with acute lymphoblastic leukemia (ALL) who had all received cranial irradiation for the prevention of central nervous system (CNS) leukemia 1-13 years previously. Children were assessed for adverse late effects of their therapy, using age-appropriate Wechsler measures of overall intellectual ability and supplementary tests. Forty-five siblings near in age to the patients were tested as controls. The patients who had had the most intensive central nervous system (CNS) prophylaxis were found to have a WISC-R Full Scale IQ 17 points lower than the sibling control group. Performance IQ was more affected than verbal IQ. The patients were more easily distracted and less able to concentrate. The severity of the aftereffects was related to younger age at the time of CNS prophylaxis and to a higher dose of cranial irradiation but not to time since CNS prophylaxis. CNS prophylaxis using a combination of cranial irradiation and intrathecal methotrexate has lowered the incidence of CNS relapse in childhood ALL but is associated with considerable long-term morbidity in survivors.     

Cognitive and Academic Late Effects Among Children Previously Treated for Acute Lymphocytic Leukemia Receiving Chemotherapy as CNS Prophylaxis

Objective: Examine cognitive and academic late effects amongchildren and adolescents who had received central nervous system(CNS) prophylactic chemotherapy alone for acute lymphocyticleukemia (ALL); none had received whole brain radiation therapy(RT). Method: Subjects included 47 children and adolescents from 5to 22 years of age who were treated on the same protocol andhad been off treatment from 2 to 7 years at the time of assessment. Results: As a group the survivors displayed generally averageperformance on measures of cognitive and academic abilities,although they differed from normative means on tests of nonverbalskills. Girls performed more poorly than the normative sampleon nonverbal tasks, while no differences were found for boys.Age at diagnosis and time off treatment were not significantlyassociated with cognitive and academic functioning for survivorsof this particular chemotherapy-only protocol. Conclusions: Data were interpreted to support generally modestpotential late effects in specific areas for children and adolescentssurviving ALL. These findings suggest a need for monitoringnonverbal cognitive skills for childhood survivors of ALL, particularlyfor girls.     

Allogeneic Hematopoietic Cell Transplantation in Children with Relapsed Acute Lymphoblastic Leukemia Isolated to the Central Nervous System

Allogeneic hematopoietic cell transplantation (HCT) is the standard of care for pediatric patients with early medullary relapse of acute lymphoblastic leukemia (ALL). Most patients with isolated central nervous system (CNS) relapse have good outcomes when treated with intrathecal and systemic chemotherapy followed by irradiation to the neuroaxis. However, the role of HCT remains unclear for those patients with early isolated CNS relapse (<18 months) or who had high risk disease at diagnosis. We therefore compared the HCT outcomes of 116 children treated at the University of Minnesota from 1991 to 2006 with relapsed ALL involving the CNS alone (CNS, n = 14), the bone marrow alone (BM, n = 85), or both bone marrow and CNS (BM + CNS, n = 17). There were no significant differences among groups in age at diagnosis or transplant, length of first complete remission (CR1), remission status (CR2 versus ≥CR3), graft source, or preparative regimen. The incidence of acute GVHD was similar between groups. Patients with isolated CNS relapse had the lowest cumulative incidence of mortality following transplant (CNS: 0%, BM: 19%, BM + CNS: 29%, P = .03) and relapse (CNS: 0% BM: 30%, BM + CNS: 12%, at 2 years, P = .01) and highest leukemia-free survival (CNS: 91%, BM: 35%, BM + CNS: 46%, P < .01) at 5 years. Risk factors for poor survival were: T cell leukemia or BCR-ABL gene rearrangement, history of marrow relapse, and receipt of HLA-mismatched marrow. These data support the use of allogeneic HCT in the treatment of children with poor prognosis isolated CNS relapse.     

Translocation t(1;19)(q23;p13) in acute lymphoblastic leukemia. A report on six new cases and an unusual t(17;19)(q11;q13), with special reference to prognostic factors

We report clinical, immunologic, and cytogenetic characteristics of six patients with a t(1;19)(q23;p13) that was balanced in one case and of the unbalanced type [-19,der(19)t(1;19)(q23;p13)] in the remaining five cases. Intracytoplasmic immunoglobulins (cIg) were positive in the three cases where they were found. We also report on another patient, with a t(17;19) involving 17q11 and probably 19q13 regions, although involvement of 19p13 could not be excluded. In this patient, cIg were also present, thus raising the issue of whether such a rearrangement could be a variant of t(1;19). Clinically, five patients belonged to the high-risk acute lymphoblastic leukemia (ALL) group, because of high leukocytosis, central nervous system (CNS) disease at presentation, or massive organomegaly. Cytologically, all cases were FAB type L1. Except for the two cases allografted in the first complete remission (CR) all patients relapsed, three of them within 13 months. Two CNS relapses were seen in spite of adequate CNS prophylaxis. ALL with t(1;19) appears to be a poor-risk ALL subgroup and probably requires a reinforcement of therapeutic modalities that might include, when possible, allografting at first CR.     

Evaluation of cerebrospinal fluid mononuclear cells obtained from children with acute lymphocytic leukemia: advantages of combining cytomorphology and terminal deoxynucleotidyl transferase

Sixty cerebrospinal fluid (CSF) samples were obtained from 28 children with terminal deoxynucleotidyl transferase (TdT) positive acute lymphocytic leukemia (ALL). Cell morphology was evaluated using Wright's stained cytocentrifugation prepared slides. The presence of nuclear TdT was detected by an immunofluorescent (IF) assay. Evaluation of CSF mononuclear cells using these two methods simultaneously allowed us to differentiate between leukemic and nonleukemic pleocytosis. Agreement between cytomorphology and TdT in identifying CNS lymphoblasts was found in 55 of 60 samples. Seventy-two per cent of the TdT-positive samples were obtained from children with CSF cell counts less than 10 WBC/mm3. We recommend that these two methods be used in conjunction when evaluating CSF mononuclear cells from children with TdT positive ALL.     

Second cessation of therapy in children with acute lymphoblastic leukemia]

In the group of 63 children in whom a relapse of ALL after first suspension of treatment occurred, and in whom a repeated cessation of therapy had place, 46.2% of patients had probability of a prolonged symptomless survival. The children with an isolated extramedullary relapse had a greater chance for a DFS of 7 years, than those with a relapse in the bone marrow (p = 0.05). The patients with a relapse occurring after the first cessation of treatment of ALL should be treated as intensively as newly diagnosed cases, because they have a real possibility for a prolonged survival during remission phase of disease.     

Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia

Ninety-seven children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) received HLA-identical bone marrow transplants from sibling donors, after preparation with 1320 cGy of hyperfractionated total-body irradiation and high-dose cyclophosphamide. Kaplan-Meier product-limit estimates (means +/- SE) of disease-free survival at five years among patients with ALL in second remission, third remission, and fourth remission or relapse were 64 +/- 9, 42 +/- 14, and 23 +/- 11 percent, respectively, with probabilities of relapse of 13 +/- 7, 25 +/- 13, and 64 +/- 16 percent. Among patients with AML in first remission, second remission, and third remission or relapse, five-year disease-free survival estimates were 66 +/- 10, 75 +/- 15, and 33 +/- 19 percent, with respective relapse probabilities of 0, 13 +/- 12, and 67 +/- 19 percent. The most frequent cause of death in patients in early remission (ALL in second or third remission or AML in first or second remission) was bacterial sepsis, fungal sepsis, or both, most often in the presence of acute or chronic graft-versus-host disease. Among patients with ALL who received transplants while in second remission, the duration of the initial remission had no effect on the probability of relapse after transplantation. The only pretransplantation factor that significantly affected outcome was the disease status at the time of transplantation; patients in early remission had better disease-free survival. We conclude that transplantation after preparation with hyperfractionated total-body irradiation and cyclophosphamide is an effective mode of therapy in children with refractory forms of acute leukemia.     

Urinary tract infections associated with otitis media in infants and children

One hundred six infants and children with otitis media were screened for the incidence of urinary tract infections (UTI) by urine culture. Seventeen patients (16%) who had UTI were compared with the 80 patients with sterile urine for differences in host factors and laboratory features. The mean age, WBC counts, and ESR values were similar. Patients with UTI-associated otitis media had a higher incidence of hematuria. Prevalence of high (greater than or equal to 103 degrees F) fever was higher among the boys with UTI. However, because of the lack of definite clinical and laboratory clues to determine the presence or absence of UTI, urine culture is the only test to uncover otitis media patients with concomitant UTI.     

Clinical features and factors of unfavorable outcomes for non-polio enterovirus infection of the central nervous system in northern Taiwan, 1994-2003.

This study investigated the clinical manifestations and outcomes of central nervous system (CNS) infection by enteroviruses. Cases with CNS involvement among all enterovirus-culture-positive cases from January 1995 to June 2003 were retrospectively reviewed. Among 1028 enterovirus-culture-positive cases, there were 333 cases involving the CNS. Of these, the ratio of male to female subjects was 1.78, and the mean (+/- standard deviation) age was 6.83 +/- 5.9 years; 21 were premature neonates, and 10 failed to thrive. Disease entities included 282 cases of aseptic meningitis (84.7%), 44 cases of encephalitis (13.2%), and 7 cases of encephalomyelitis/polio-like syndrome (2.1%). Of these cases, 97.9% (326/333) had fever with peak body temperature at 38.9 degrees C, 85% had headache and vomiting, 70% had meningeal signs, 64% had neck stiffness, 16.6% (55/333) had change of consciousness, 5.4% (18/333) had seizures and 5.2% (17/333) had myoclonic jerks. Mannitol was administered in 77.2% of patients (257/333), along with intravenous immunoglobulin in 6.6% (22/333). Twelve cases received ventilator support. One patient died of hand-foot-and-mouth disease, encephalitis plus cardiopulmonary failure, and 2 premature neonates died of hepatic failure, disseminated intravascular coagulation, sepsis-like syndrome and myocarditis. Eighteen had neurologic sequelae, including 7 with limb weakness, 5 with epilepsy, 2 with sixth cranial nerve palsy, 3 with cerebral palsy, 4 with psychomotor retardation, 2 with spasticity, and 1 with hearing loss. Factors associated with unfavorable outcomes (death or sequelae) included younger age (p=0.0003), higher peak white blood cell count (WBC) [p=0.0009] and skin rash (p=0.005). Younger age and higher peak WBC were poor prognostic factors of severe enterovirus CNS infection. Death was related to neonatal enterovirus infection and enterovirus 71 infection in young children.     

Intellectual, neuropsychological, and academic functioning in long-term survivors of leukemia

OBJECTIVE: To assess the effects of treatment for acute lymphoblastic leukemia (ALL) on children's cognitive functioning. METHOD: Participants were long-term survivors of ALL treated with cranial irradiation and central nervous system (CNS) chemotherapy (n = 20), or CNS chemotherapy only (n = 21), healthy children (n = 21), and children with chronic asthma (n = 21). The groups were compared on measures of intellectual, neuropsychological, and academic functioning. RESULTS: CNS chemotherapy, with and without cranial irradiation, was associated with significantly lower levels of intellectual and academic functioning. Children with chronic asthma obtained lower scores than healthy controls, but these differences were not significant. Tests of neuropsychological functioning did not consistently separate the groups. CONCLUSIONS: CNS chemotherapy and, to a lesser extent, chronic illness both contribute to the poorer performance of long-term survivors of ALL on measures of intellectual and academic functioning.     

Cytogenetic findings in congenital leukemia: case report and review of the literature

The cytogenetic findings in a five-week-old female infant with acute lymphoblastic leukemia (ALL) are reported. Markers 11q - and 19 + were observed and considered to be due to an interstitial deletion of segment 11q13 to 11q23 of chromosome #11 and an insertion of this segment into the terminal region of the short arm of #19. Previously published banded cases of leukemic infants under one year of age have been summarized. A review of the data in these 29 cases suggests that the appearance of a normal karyotype in acute leukemia of infants (less than or equal to 1 year old) is much less common than in other categories of acute leukemia. Fourteen out of 29 cases (48%) had chromosomal abnormalities involving 11q. Seven of eight ALL cases had aberrations with a breakpoint at 11q22-23; six cases had t(4;11), one case had a del(11q) and ins(19p), and another had a t(1;22;4). All of three AMMoL cases had translocations involving the long arm of #11. The percentage of patients with t(4;11) and certain translocations involving 11q in infants with ALL or AMMoL, respectively, is higher than that seen in ALL and AMMoL in general. Eleven out of 12 cases (92%) of infant acute leukemias with chromosomal abnormalities involving 11q22-23 were five months old or less.     

Malformations and minor anomalies in children whose mothers had prenatal diagnosis: comparison between CVS and amniocentesis

The frequency of abortion following chorionic villus sampling (CVS) is similar to that following amniocentesis. However, there is no information on long-term effects, such as malformations in liveborn children exposed to CVS. We evaluated 189 infants whose mothers had either CVS or amniocentesis as participants in the Canadian Collaborative Randomized Trial, a prospective assessment of the safety of CVS compared with amniocentesis. The participation rate of children who could be contacted was 95%. Ninety-five of the 189 infants (50.2%) had been exposed to CVS, 87 (46%) to amniocentesis, and 7 (3.8%) to both. (The latter group was excluded from calculations.) One hundred twenty-eight (128) children had greater than or equal to one minor anomalies but no major abnormalities: 58 of 95 (60%) in the CVS and 70 of 87 (80%) in the amniocentesis group. Twenty-six children had malformations: 17 (17.8%) in the CVS and 9 (10.3%) in the amniocentesis group. Only one anomaly, Sturge-Weber dysplasia (amniocentesis group), was potentially severe and none were life-threatening. Superficial cavernous hemangiomas (strawberry nevi) were noted more frequently in children in the CVS group (12.6%) than in the amniocentesis group (3.4%), but only slightly higher than in the general public. We conclude that exposure to CVS is not associated with an increased frequency of malformations or minor anomalies in infants compared with amniocentesis although we observed a higher frequency of superficial cavernous (strawberry) hemangiomas in the children in the CVS group.     

Long-term developmental outcome of infants with iron deficiency

BACKGROUND. Iron-deficiency anemia has been associated with lowered scores on tests of mental and motor development in infancy. However, the long-term developmental outcome of infants with iron deficiency is unknown, because developmental tests in infancy do not predict later intellectual functioning. METHODS. This study is a follow-up evaluation of a group of Costa Rican children whose iron status and treatment were documented in infancy. Eighty-five percent (163) of the 191 children in the original group underwent comprehensive clinical, nutritional, and psychoeducational assessments at five years of age. The developmental test battery consisted of the Wechsler Preschool and Primary Scale of Intelligence, the Spanish version of the Woodcock-Johnson Psycho-Educational Battery, the Beery Developmental Test of Visual-Motor Integration, the Goodenough-Harris Draw-a-Man Test, and the Bruininks-Oseretsky Test of Motor Proficiency. RESULTS. All the children had excellent hematologic status and growth at five years of age. However, children who had moderately severe iron-deficiency anemia as infants, with hemoglobin levels less than or equal to 100 g per liter, had lower scores on tests of mental and motor functioning at school entry than the rest of the children. Although these children also came from less socioeconomically advantaged homes, their test scores remained significantly lower than those of the other children after we controlled for a comprehensive set of background factors. For example, the mean (+/- SD) adjusted Woodcock-Johnson preschool cluster score for the children who had moderate anemia in infancy (n = 30) was 448.6 +/- 9.7, as compared with 452.9 +/- 9.2 for the rest of the children (n = 133) (P less than 0.01); the adjusted visual-motor integration score was 5.9 +/- 2.1, as compared with 6.7 +/- 2.3 (P less than 0.05). CONCLUSIONS. Children who have iron-deficiency anemia in infancy are at risk for long-lasting developmental disadvantage as compared with their peers with better iron status.     

Chronic kidney disease care delivered by US family medicine and internal medicine trainees: results from an online survey

Background

Procedural pain relief is sub-optimal in infants, especially small and vulnerable ones. Tetracaine gel 4% (Ametop^®, Smith-Nephew) provides pain relief in children and larger infants, but its efficacy in smaller infants and for peripherally inserted central catheters (PICC) remains uncertain. The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight (VLBW) infants during insertion of a PICC.

Methods

Medically stable infants greater than or equal to 24 weeks gestation, requiring a non-urgent PICC, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. The PICC was inserted according to a standard protocol. Pain was assessed using the Premature Infant Pain Profile (PIPP). A 3-point change in the pain score was considered clinically significant, leading to a sample size of 54 infants, with 90% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test.

Results

Fifty-four infants were included, 27 +/- 2 weeks gestation, 916 +/- 292 grams and 6.5 +/- 3.2 days of age. Baseline characteristics were similar between groups. The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group (difference 0.86, 95% CI -1.86, 3.58). Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group (difference -78, 95% CI -539, 117). Local skin erythema was observed transiently in 4 infants (3 in the treatment and 1 in the placebo group). No serious harms were observed.

Conclusion

Tetracaine 4% when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants.     

Prognostic significance of the Philadelphia chromosome in acute lymphocytic leukemia

Prognostic factors for acute lymphocytic leukemia (ALL), including initial white blood count (WBC), age at diagnosis, sex, cytology, lymphocyte surface markers, and glucocorticoid receptors, have been evaluated in 12 patients presenting with ALL and the Philadelphia chromosome (Ph¹+ ALL). Ph¹+ ALL patients had a median initial WBC of 89 × 10⁹ liter, a median age of 23 years and a male: female ratio of 1:1. The cytology of the blasts was L1 in 50% and L2 in 50%. The blasts in all cases studied were characteristic of non-T, non-B, common ALL, had high terminal deoxynucleotidyl transference levels, and low numbers of glucocorticoid receptors. The prognostic factors in these Ph¹+ ALL patients were compared with those of a concurrent group of adults with Ph¹? ALL. Patients with Ph¹+ ALL more commonly had unfavorable prognostic features (high WBC, older age, male sex, L2 cytology, and low glucocorticoid receptors). They also had fewer complete remissions (58 vs. 100%, p=0.07), shorter remission durations (median 10 vs. 44+ months, p=0.001) and shorter survival times (median 11 vs. 48.5+ months, p=0.00008). However, even when patients with similar prognostic features were compared, those with the Ph¹ had fewer and shorter remissions and shorter survival times than ALL patients without the Ph¹. These data suggest that the Ph¹ is an independent unfavorable prognostic factor in adults with ALL.     

Detection of specific local immunity factors in children with herpetic diseases of the oral mucosa

Specimens of mixed untreated saliva from 3 groups of children were tested for antibodies to herpes virus by the fluorescent antibody technique (33 children with acute herpes stomatitis, 64 with recurrent herpes stomatitis, and 30 in the control group). Herpes virus antibodies were found in the saliva in 27.2 +/- 7.7% of the cases at the peak of acute stomatitis and in 77.7 +/- 10.0% of cases in the period of epithelization, in 84.6 +/- 10.0% of the examined subjects the antibodies were detected 2-4 months after the disease. Examinations of 64 saliva specimens obtained from the children during one of the relapses of chronic stomatitis demonstrated antibodies more frequently (59.3 +/- 8.0%) than in children at the peak of acute stomatitis disease. A trend for increased antibody content in the saliva of children by the period of epithelization of lesions in the buccal cavity both in acute stomatitis and during relapses of chronic disease was observed. No herpes antibodies were found in saliva specimens from 30 children of the control group.