Lymphocytic Leukemia In Remission Research Articles

S1809 Portal Cavernoma Cholangiopathy Presenting With Acute Cholangitis

Introduction: Portal cavernoma cholangiopathy (PCC) is defined as abnormalities in the biliary tree due to a portal cavernoma. Most cases occur in non-cirrhotic patients who remain asymptomatic. 5-30% of patients develop symptomatic disease and only 8% of symptomatic cases present with acute cholangitis. This case describes PCC as an uncommon cause of acute cholangitis. Case Description/Methods: A 26-year-old male with a medical history of acute lymphocytic leukemia in remission, cryptogenic cirrhosis, and portal vein thrombosis (PVT) on warfarin presented with 2-weeks of worsening abdominal pain, darkening of the urine, and weight loss. On examination, he was febrile to 101°F, normotensive, and had both scleral and palatal icterus. Initial labs revealed White blood count: 13.5 x10(3)/mcL, total bilirubin 7.5mg/dL, & ALP 398U/L. MRCP showed biliary dilation related to extensive portal vein cavernous transformation and narrowing in the common bile duct (CBD) due to compression by cavernous vessels in porta hepatis (Figure). Endoscopic ultrasound (EUS) showed PVT and collateral flow. Endoscopic retrograde cholangiopancreatography (ERCP) revealed biliary narrowing and beading. These findings were diagnostic of cavernous transformation with cholangiopathy. The patient improved after biliary stent placement with repeat stenting 6 months later. There was a discussion about TIPS and Portal vein reconstruction. However, the patient did not follow through. Discussion: PCC develops through PVT-related ischemia that underlies the development of collateral flow, biliary stricture, and dysmotility predisposing patients to cholangitis. Management is only indicated with symptomatic disease with endoscopic and surgical intervention. We report a rare presentation of PCC successfully managed with ERCP.Figure 1.: A) MRCP: Cavernous transformation of the portal vein. B) EUS: A portal vein thrombus involving area of portal vein confluence and collateral flow consistent with cavernous transformation. C) ERCP: Abnormal areas of narrowing and beading throughout the biliary system with extrinsic stenosis.

S1803 Extramammary Paget’s Disease of the Anal Canal: A Rare Diagnosis

INTRODUCTION: Extramammary Paget's disease (EMPD) is an uncommon intraepithelial malignancy that often involves areas of skin with high apocrine gland density. Cases of EMPD involving the anal canal are extremely rare. We present a case of anal EMPD where subsequent work up was unsuccessful in locating the primary site of the associated gastrointestinal (GI) cancer. CASE DESCRIPTION/METHODS: 76 year old male with history of diabetes, hypertension, immune thrombocytopenic purpura treated with rituximab, and chronic lymphocytic leukemia in remission after treatment with chemotherapy, presented with chronic constipation. He denied hematochezia, weight loss, or family history of GI malignancy. He underwent colonoscopy where one polyp was removed from the cecum with pathology revealing a tubular adenoma as well as a one centimeter whitish area of abnormal-appearing mucosa in the anal canal extending proximally into the anal transition zone and initial biopsy demonstrated invasive EMPD (BerEP4, CK7, CK20 & mucicarmine positive) (Image 1). A second biopsy of the lesion showed anal intraepithelial neoplasia (AIN 2–3) with EMPD (CK7, CK20, CDX2 & mucicarmine positive) (Image 2). Later, PET/CT scan showed linear FDG uptake in the anorectal region and several FDG-avid lymph nodes in the right external iliac chain and inguinal region. Subsequent excisional biopsy of the right inguinal lymph nodes showed metastatic tumor, with an immunohistochemistry profile similar to prior EMPD biopsies (Image 3). Patient underwent a repeat colonoscopy which did not reveal any new findings. An EGD and capsule endoscopy were also done which did not show any suspicious masses or lesions. Wide local excision with lymph node dissection was recommended, but the patient declined further management. Two months later, the patient got a CT abdomen and pelvis due to increasing abdominal pain which showed worsening metastatic disease in the liver and abdominal lymph nodes. Patient opted for hospice care and died a few weeks afterwards. DISCUSSION: To our knowledge, EMPD involving the anal canal is a rare finding with only a handful of cases reported in the literature. It was an incidental diagnosis and most likely associated with an unidentified colorectal adenocarcinoma. Surgery is the treatment of choice for localized disease, provided there is no evidence of dermal invasion or distant metastasis. Radiation and chemotherapy may be trialed in advanced cases, but efficacy remains poor.Figure 1.: Colonoscopy (A &B) showing mucosal lesion in anal canal (arrows), extending proximally into the anal transition zone. Anus biopsy on H & E stain (C ) showing invasive extramammary Paget’s disease with nests of malignant epithelial cells showing a high nuclear-to-cytoplasmic ratio with arrows indicating invasive carcinoma which is confirmed with BerEP4 immunohistochemistry stain (D) confirming in situ (red arrows) and invasive extramammary Paget's disease (blue arrows).Figure 2.: Anus biopsy (20X) with H & E stain (B) showing foci of extramammary Paget’s disease (black arrows) in tissue composed of high grade anal intraepithelial neoplasia (AIN 2-3). CDX2 immunohistochemistry stain (C) and Mucicarmine stain (D) highlighting extramammary Paget's disease.Figure 3.: PET/CT (A) shows FDG-avid lymph nodes in the right external iliac chain and inguinal region (white arrow). Right inguinal lymph node biopsy shows metastatic extramammary Paget's disease (40X) with H & E stain (B), confirmed with CK 7 immunohistochemistry stain expression (10X) in (C) and CDX2 immunohistochemistry expression (40X) in (D).

PF391 INFLUENCE OF ATORVASTATIN THERAPY ON GALECTIN‐3, VE‐CADHERIN, AND CARDIOVASCULAR RISK IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

Background:The vast majority of chronic lymphocytic leukemia survivors experience late effect of treatment including cardiovascular events. These effects contribute most of the substantial effects excess mortality in patients with full or partial response to CLL treatment.Aims:We aimed to evaluate the impact of atorvastatin on galectin‐3 and VE‐cadherin, and cardiovascular risk in patients with chronic lymphocytic leukemia in remission.Methods:One hundred fifty seven out subjects with chronic lymphocytic leukemia in full or partial remission were enrolled in the study. Atorvastatin at doses 20 mg/d and 40 mg/d was prescribed for patients with hypercholesterinemia, dyslipidemia, coronary artery disease risk factors. Blood samples for biomarkers measurements were collected at the visit of inclusion into the study. Plasma levels of galectin‐3, and VE‐cadherin were measured by ELISA method at baseline and after 1 year of observation period.Results:Two hundred seventy cumulative clinical events occurred in 68 patients (43.3%) within the follow‐up, with their distribution being as follows: 12 deaths for cardiovascular reasons, 17 life‐threatening arrhythmias, 36 cardiac ischemic events, 9 strokes, 38 decompensated chronic heart failures, and 58 hospital admissions for cardiovascular reasons. Patients were divided to two groups depending on the atorvastatin treatment. At baseline there were no difference in levels of biomarkers between groups. In one year there were significant differences in levels of galectin‐3 (8,86 ± 5,62 ng/ml vs 16,74 ± 8,52 ng/ml; р = 0,035), VE‐cadherin (0,76 ± 0,64 ng/ml vs 2,19 ± 1,66 ng/ml; р = 0,046) in the group without atorvastatin treatment. The optimal cut‐off point of galectin‐3 level for distinguishing high cardiovascular risk patients from low risk ones was 11.75 ng/ml, with a sensitivity of 70.4% and a specificity of 96.8%; for VE‐cadherin – 0.53 ng/ml, with a sensitivity of 72.6% and a specificity of 95.2%. Combination of galectin‐3 and VE‐cadherin had high negative prognostic value (93.4%) for evaluation of cardiovascular events.Atorvastatin treatment were associated with decreasing of cumulative cardiovascular events with appearance of early differences between groups during 3 year observation time (long‐rank test, χ2 = 11,775, р = 0,001). During first year of observation event‐free survival were better for patients treated with atorvastatin 40 mg/d in comparing to patients treated with atorvastatin 20 mg/d (long‐rank test, χ2 = 6,147, р = 0,013).Summary/Conclusion:Among patients with chronic lymphocytic leukemia in remission galectin‐3 and VE‐cadherin are associated with increased risk of cardiovascular events within 3 year observation period. Atorvastatin prevents increasing of galectin‐3 and VE‐cadherin and reduces risk of cardiovascular events in this group of patients. It was proposed to prescribe atorvastatin to patients with level of galectin‐3 11.75 ng/ml or higher, and/or level of VE‐cadherin 0.53 mg/ml or higher for prevention of cardiovascular events during 3 year period.

Atorvastatin influence on cardiac function and rhythm variability in patients with chronic lymphocytic leukemia in remission

Purpose – to evaluate atorvastatin influence on cardiac hemodynamics and rhythm variability in patients with chronic lymphocytic leukemia (CLL) in remission.Materials and methods. One hundred fifty-seven subjects with chronic lymphocytic leukemia in full or partial remission were enrolled in the study. Atorvastatin at doses 20 mg/d and 40 mg/d were prescribed for patients with hypercholesterinemia, dyslipidemia, coronary artery disease risk factors. All patients and control subjects underwent echocardiography, and 24-hour Holter monitoring with continuous time-dependent and spectral analysis of heart rate variability at baseline, after 1 year and after 3 years of observation period. Cardiovascular events were evaluated for 3 years observation period.Results. In one year after reaching remission of CLL in comparing with baseline there is a statistical decrease in E (0.98 ± 0.15 м/с and 0.89 ± 0.16 м/с; P < 0.001), A (0.98 ± 0.16 м/с and 0.92 ± 0.15 м/с; p=0.023). E/A (P = 0.011) were significantly lower in group of patients without atorvastatin treatment (P = 0.011) and in group treated with atorvastatin in dose 20 mg a day (P = 0.002). In three year EF decreased in comparing with baseline (55.43 ± 4.75 % and 51.52 ± 6.40 % і; P = 0.009) in patients without atorvastatin treatment.In three year global circular systolic strain (-17.42 ± 3.24% and -16.78 ± 3.56 %; P = 0.035), global longitudinal systolic strain (-18.13 ± 2.15 % and -17.04 ± 2.07 %; P = 0.008), global longitudinal systolic strain rate (-1.03 ± 0.23с-1 and -0.91 ± 0.33с-1; P = 0.024) were significantly decreased in patients without atorvastatin treatment. The LF values of group of patients treated without atorvastatin of patients were significantly lower than those of controls, and HF values of patients with CLL (P = 0.043) and HNL (P = 0.04) were lower.Conclusions. Among patients with chronic lymphocytic leukemia in remission systolic and diastolic function, regional systolic contractility and variability of cardiac rhythm were significantly worse in three year especially in patients without atorvastatin treatment.

Influence of atorvastatin therapy on biological markers and cardiovascular risk in patients with chronic lymphocytic leukemia in remission

Purpose – to assess the impact of atorvastatin on plasma biomarkers and cardiovascular risk in patients with chronic lymphocytic leukemia in remission. Materials and methods. A total of 157 subjects with chronic lymphocytic leukemia in complete or partial remission were enrolled in the study. Atorvastatin at doses 20 mg/d and 40 mg/d were prescribed for patients with hypercholesterinemia, dyslipidemia and risk factors for coronary artery disease. Blood samples were collected for measurements of biomarkers such as galectin-3, VE-cadherin, VEGF-1, sCD40L, NT-proBNP and interleukin-6 by ELISA method at the time of inclusion into the study and after a 1-year follow-up. Cardiovascular events occurrence was assessed throughout a 3-year follow-up. Results. There were 170 clinical events occurred in 68 patients (43.3 %) within the follow-up, with the following distribution: 12 cardiovascular deaths, 17 life-threatening arrhythmias, 36 cardiac ischemic events, 9 strokes, 38 cases of chronic heart failure decompensation, and 58 hospital admissions for cardiovascular reasons. Patients were divided into two groups depending on the atorvastatin treatment. There were no differences in baseline levels of biomarkers between groups. Significant differences were observed in levels of galectin-3 (8.86 ± 5.62 ng/ml vs 16.74 ± 8.52 ng/ml; P = 0.035), VE-cadherin (0.76 ± 0.64 ng/ml vs 2.19 ± 1.66 ng/ml; P = 0.046) only in the group without atorvastatin treatment in the 1-year follow-up. Significant differences in levels of VEGF-1, IL-6, sCD40L, NT-proBNP were not revealed between groups during observation time. Atorvastatin treatment was associated with decreased cumulative cardiovascular event incidence with early differences in their occurrence between groups during the 3-year follow-up (log-rank test, χ 2 = 11.775, P = 0.001). Event-free survival were better in patients treated with atorvastatin 40 mg/d in comparison to patients treated with atorvastatin 20 mg/d (log-rank test, χ 2 = 6.147, P = 0.013) during the first year of follow-up. Conclusions. Among patients with chronic lymphocytic leukemia in remission, the key biomarkers of angiogenesis such as galectin-3 and VE-cadherin are associated with increased risk of cardiovascular events within 3-year follow up. Atorvastatin prevents an increase in angiogenesis biomarkers and reduces risk of cardiovascular events in this group of patients.

Interactions between galectin-3 and cardiovascular risk in patients with chronic lymphocytic leukemia in remission: results of 3-year prospective study

Purpose – to evaluate interactions between the value of circulating galectin-3 and cardiovascular risk in patients with chronic lymphocytic leukemia in remission. Materials and methods. One hundred fifty seven out subjects with chronic lymphocytic leukemia in full or partial remission were enrolled in the study. Observation period was up to 12 months. Blood samples for biomarkers measurements were collected at the visit of inclusion into the study. ELISA method for measurements of circulating level of galectin-3 was used. Cardiovascular events were evaluated for 3 year observation period. Results. Two hundred seventy cumulative clinical events occurred in 68 patients (43.3 %) within the follow-up, with their distribution being as follows: 12 deaths for cardiovascular reasons, 17 life-threatening arrhythmias, 36 cardiac ischemic events, 9 strokes, 38 decompensated chronic heart failures and 58 hospital admissions for cardiovascular reasons. Mean levels of galectin-3 in free-events subject cohort and subjects cohort with cardiovascular events were 5.22 ± 3.06 ng/ml and 12.64 ± 5.24 ng/ml (Р < 0.0001). In patients after antitumor treatment with anthracyclines mean levels of galectin-3 were higher in comparing with patients after antitumor treatment without anthracyclines (Р = 0.0014). There were no differences in the value of galectin-3 in depend on gender, age, cumulative dose of anthracyclines, arterial hypertension, hyperlipidemia, diabetes mellitus, body mass index, smoking. Conclusions. Among patients with chronic lymphocytic leukemia in remission increased circulating galectin-3 associates with presence of anthracyclines in antitumor treatment and increased cumulative cardiovascular events within 3 year observation period.

Value of circulating galectin-3 for prognosis of cardiovascular events in patients with chronic lymphocytic leukemia in remission

Мета роботи – виявлення прогностичної значущості циркулюючого галектину-3 у виникненні кардіоваскулярних подій, виживаності пацієнтів із хронічною лімфоцитарною лейкемією в ремісії. У дослідження були включені 156 пацієнтів із хронічною лімфоцитарною лейкемією в ремісії, період спостереження становив 12 місяців. Рівень циркулюючого галектину-3 визначали за допомогою імуносорбентного методу. Гемодинамічні показники оцінювали за допомогою ехокардіографії. Зафіксували 216 кардіоваскулярних подій у 51 пацієнта (32,7%): 7 смертей, 122 кардіальних аритмій, 16 ішемічних подій, 3 інсульти, 30 випадків виникнення хронічної серцевої недостатності, 38 госпіталізацій, що пов’язані з кардіоваскулярними причинами. Медіана циркулюючого VE-галектину в пацієнтів без кардіоваскулярних подій і в пацієнтів із кардіоваскулярними подіями становила 5,16нг/мл (95% довірчий інтервал [ДІ] = 4,74-5,56нг/мл) і 16,40нг/мл (95% ДІ = 14,80-18,01нг/мл) відповідно (р<0,001). Мультиваріантний регресійний аналіз показав, що циркулюючий галектин-3 є незалежним прогностичним фактором виникнення кардіоваскулярних подій (відношення шансів 1,13; 95% ДІ = 1,07-1,25; р=0,003) протягом одного року. Серед пацієнтів із документованою хронічною лімфоцитарною лейкемією в ремісії підвищення циркулюючого галектину-3 асоціюється з виникненням кардіоваскулярних подій протягом одного року.

West Nile Virus Infection in a Teenage Boy With Acute Lymphocytic Leukemia in Remission

West Nile Virus Infection in a Teenage Boy With Acute Lymphocytic Leukemia in Remission

West Nile Virus Infection in a Teenage Boy With Acute Lymphocytic Leukemia in Remission

West Nile Virus (WNV) infection is an important cause of encephalitis. Although the medical literature contains examples of WNV encephalitis in susceptible, mainly elderly, immunocompromised hosts, few case reports have described pediatric cases. The authors describe an adolescent with acute lymphocytic leukemia and WNV encephalitis. Surveillance studies indicate an increase in WNV activity. Physicians need to be aware of WNV activity in their community and consider WNV as a potential source of infection.

Interferon maintenance therapy for patients with chronic lymphocytic leukemia in remission after fludarabine therapy

Many patients with chronic lymphocytic leukemia (CLL) achieve remission after treatment with fludarabine chemotherapy. Most of these patients, however, later experience relapse. In addition, immunologic deficits may persist even in patients in complete remission; lymphopenia, predominantly involving the CD4 population, is universal after fludarabine therapy. We used recombinant alpha interferon (IFN-alpha) maintenance therapy in patients with CLL who achieved remission in response to fludarabine therapy to determine its effect on residual disease, assessed by either bone marrow biopsy or flow cytometry, and on immune restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by subcutaneous injection three times weekly). Twenty-two patients (71%) were in complete remission (CR) and nine (29%) were in partial remission (PR). Of the 22 patients in CR, 21 (95%) had evidence of residual disease at the start of IFN-alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in 45%, and anergy or hypoergy in 52%. Only one patient in PR achieved a CR on IFN-alpha therapy: the only patient who had had no prior fludarabine but had been treated with chlorambucil and prednisone. All patients in CR with minimal residual disease had persistent disease after IFN-alpha treatment. There were no increases in CD4 counts or IgG levels; three patients with borderline responses to skin testing had an increase in the number of positive tests while on IFN-alpha. The time to progression was no different in patients treated with IFN-alpha than in a historical control group of patients who had received no further therapy after fludarabine. In summary, the use of IFN-alpha maintenance did not eradicate residual disease, restore immune function, or prolong remissions in patients with CLL responsive to fludarabine.

Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma

We analyzed the relevance of HLA incompatibility to acute graft-versus-host disease, relapse, and survival in 281 patients with hematologic neoplasms who underwent bone marrow transplantation. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A,-B, and -D antigens of the haplotype not shared: 29 were phenotypically identical, 119 were incompatible for one locus, 104 for two loci, and 29 for three loci. These 281 patients were compared with 967 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. Occurence of severe acute graft-versus-host disease was evaluated in patients who achieved sustained engraftment. In recipients of haploidentical grafts of severe acute graft-versus-host disease was associated with (1) graft-versus-host disease prophylaxis containing the combination of methotrexate plus cyclosporine versus standard methotrexate, relative risk = 0.35; 95% confidence interval, 0.21–0.57, p<0.0001; and (2) the degree of recipient HLA incompatibility, relative risk = 1.95 for each locus incompatible; 95% confidence interval, 1.52–2.50, p < 0.0001; (3) patient age, relative risk = 1.23 per deacde; 95% confidence interval, 1.05–1.44, p = 0.0094. Acute graft-versus-host disease was associated with lower leukemic relapse after transplant in patients with acute lymphocytic leukemia, and chronic graft-versus-host disease was associated with lower relapse after transplant for acute nonlymphocytic leukemia in relapse or chronic myelogenous leukemia in blast crisis. After transplantation for acute nonlymphocytic leukemia in remission, chronic myelogenous leukemia in chronic phase, or acute lymphocytic leukemia in remission, the rate of leukemia relapse was 22% in 61 recipients of “one-locu” (A, B, or D)-incompatible grafts compared to 37% in 561 recipients of HLA-identical sibling grafts. Survival was decreased as the degree of HLA disparity increased. Survival of “one-locus”-incompatible transplant recipients, however, was equivalent to that of HLA-identical sibling transplant recipients.

Antipolio prophylaxis of immunocompromised children during a nationwide oral poliovaccine campaign

A nationwide vaccination campaign with oral poliovirus vaccine was organized in Finland in 1985 to halt an outbreak of poliomyelitis. Immunocompromised persons and their household contacts were excluded from the oral poliovirus vaccine target group and given instead a dose of inactivated poliovirus vaccine. This gave us an opportunity to determine whether immunocompromised persons are protected from poliomyelitis during an outbreak and oral poliovirus campaign. Fourteen children, ages 3 to 17 years, with leukemia were given a booster dose of a novel high antigen content, trivalent inactivated poliovirus vaccine. All but two responded by an at least 4-fold increase in serum-neutralizing antibodies to at least one poliovirus serotype. These results indicate that children with acute lymphocytic leukemia in remission respond well to a booster dose of inactivated poliovirus vaccine. Antibody concentrations to the uncommon local epidemic strain of type 3 poliovirus remained, however, relatively low in most patients (median, 1:6) suggesting relatively impaired heterologous response to vaccination. Possible spread of live vaccine viruses to the inactivated poliovirus-vaccinated children and their close contacts was evaluated by examining weekly fecal specimens from 20 children and their 19 regular adult contacts for cytopathic viruses. No polioviruses were isolated from 224 specimens examined, indicating that this high risk population was well-protected from unintended exposure to live polioviruses.

Body composition changes in marrow transplant recipients receiving total parenteral nutrition.

Nine patients with acute lymphocytic leukemia in remission, aged 12-35 years, undergoing allogeneic bone marrow transplantation (BMT) were studied for changes in body fluid balance and body composition. Body composition and fluids were assessed the first 4 weeks following BMT, using isotope dilution and anthropometry. Oral and parenteral nutrient intakes were recorded daily. Tracer dilution techniques were used to assess body fluid volumes and estimate body cell, lean body, and body fat masses. Body cell mass was lost (mean -1.62 kg, P less than 0.05) without significant changes in body fat or lean body masses. There was an expansion of the extracellular fluid compartment (mean +0.8 l, P less than 0.05) and a loss in the intracellular fluid compartment (mean -1.3 l, P less than 0.05) with little change in total body water volume. Changes in body weight correlated poorly with body cell mass or fluid volume changes. Change in arm muscle area correlated well with changes in body cell mass (r = 0.61, P less than 0.05) and lean body mass (r = 0.68, P less than 0.05), while that of arm fat area did not reflect its isotope dilution-derived counterpart. Instead, the change in arm fat area was related to shifts in fluid compartments. Prealbumin decreased significantly (mean -9.3 mg/dl, P less than 0.05), while albumin decreased slightly (mean -0.1 mg/dl), and both were related to changes in body cell mass. Nitrogen balance was negative throughout the study and the overall mean was related to the change in body cell mass (r = 0.60, P less than 0.05). Calorie and protein intakes were not associated with the changes in body composition, implying other causal factors.

Cerebrospinal Fluid Biogenic Amine Metabolites in Children during Treatment for Acute Lymphocytic Leukemia

To learn more about the impact of intrathecal methotrexate and cytosine arabinoside therapy on neuronal metabolism, we measured serial cerebrospinal fluid concentrations of homovanillic acid and 5-hydroxyindoleacetic acid, major metabolites of the neurotransmitters dopamine and serotonin, in children with acute lymphocytic leukemia. Multiple sequential cerebrospinal fluids were obtained from 30 children with acute lymphocytic leukemia evaluated prospectively from the time of diagnosis. We focused on the period of induction and intensification when children received weekly intrathecal chemotherapy. Paired cerebrospinal fluid specimens were also obtained at 3-month intervals from 60 children with acute lymphocytic leukemia in remission. Homovanillic acid and 5-hydroxyindoleacetic acid were measured using high performance liquid chromatography with electrochemical detection. We found that pretreatment metabolite values were no different from those in age-matched subjects in remission. In the first 5 wk of treatment, there were no significant changes in metabolite levels in patients treated exclusively with methotrexate. There was a transient decrease in homovanillic acid (-28 +/- 10%, p less than 0.001, Student's t test) and 5-hydroxyindoleacetic acid (-28 +/- 12%, p less than 0.05) in five of six patients after a single intrathecal dose of cytosine arabinoside. In the next 4 wk there was a gradual rise in levels of homovanillic acid (p = 0.001, by analysis of variance) and 5-hydroxyindoleacetic acid (p = 0.029, analysis of variance); this pattern did not correlate with administration of cranial irradiation. In children in remission, there were no significant changes in metabolite levels over a 3-month period.(ABSTRACT TRUNCATED AT 250 WORDS)

Hodgkinʼs Disease in a Child with Acute Lymphocytic Leukemia in Remission

Hodgkinʼs Disease in a Child with Acute Lymphocytic Leukemia in Remission

Lennox Syndrome in a Patient with Acute Lymphocytic Leukemia in Remission

Lennox Syndrome in a Patient with Acute Lymphocytic Leukemia in Remission

871 ACYCLOVIR THERAPY OF PRIMARY VARICELLA IN LEUKEMIA

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is an acyclic nucleoside analogue with in vitro activity against herpesviruses including varicella-zoster virus. Acyclovir has had little toxicity except for occasional bullae secondary to drug extravasation. We report our uncontrolled experience with this agent in four children with acute lymphocytic leukemia in remission and disseminated primary varicella with involvement of liver, lungs, CNS, and evidence of myelosuppression and coagulopathy. Progressive organ dissemination of varicella was present in each patient, with new skin lesions in 2, despite three daily infusions of adenine arabinoside (Ara-A). Ara-A was discontinued and IV acyclovir begun at the dose of 500 mg/M2 every 8 hours. Clinical improvement beginning within 24 hours of initiation of acyclovir with subsequent complete recovery following 7-10 days of drug occurred in 3 of 4 patients. The remaining patient, who manifested the most severe CNS, hepatic, and pulmonary dysfunction, ceased developing new skin lesions after acyclovir was begun but showed continued CNS and pulmonary deterioration with DIC, and died after three days. We observed no toxicity except for cutaneous bullae in one patient. This experience suggests that acyclovir may play a role in the treatment of disseminated primary varicella in immunocompromised hosts. Further controlled therapeutic trials with this agent are indicated.

Immunity to Diphtheria, Pertussis, Tetanus, and Poliomyelitis in Children with Acute Lymphocytic Leukemia After Cessation of Chemotherapy

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N = 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.

Legionnaires' Disease in a Child with Cancer

Although Legionnaires' disease has only recently been recognized as a distinct clinical entity, serologic surveys of localized outbreaks of respiratory illnesses have indicated that its geographic distribution is wide.1-5 Most cases have occurred in clusters, but reports of sporadic cases are increasing.6 The disease appears to be most prevalent among elderly persons or adults undergoing immunosuppressive therapy; it has seldom been documented in children.1,7,8 We report a previously undetected case of Legionnaires' disease in a child with acute lymphocytic leukemia in remission. MATERIALS AND METHODS To determine whether Legionnaires' disease had occurred in a childhood cancer population with pneumonia, we reviewed the records of patients between 1 and 18 years of age for whom percutaneous transthoracic lung aspirates had been obtained between April 1970 and December 1977.

Factors in the cryopreservation of bone marrow cells from children with acute lymphocytic leukemia

Abstract Bone marrow cells from 42 children with acute lymphocytic leukemia in remission and 19 normal adults were preserved in liquid nitrogen for periods of up to 50 weeks. Many factors in the process of cryopreservation were investigated in an attempt to optimize the recovery of the bone marrow colony forming cells. The effect of cryopreservation on the cells which produce colony stimulating activity also was investigated. With optimization of this technique, it was observed that approximately 100% of the bone marrow nucleated cells were recovered and approximately 50% of the total colony forming cells were viable after 50 weeks in liquid nitrogen.