HEMATOLOGY AND ONCOLOGY

NEUTROPENIA IN THE PEDIATRIC POPULATION AND ITS a- BONE MARROW TRANSPLANTATION (BMT) IN GAUCHER'S DIS- EASE. Charles S. Au ust, Michael Palmieri, Peter ASSOCIATION WITH 1,;YECTION. R. Bowden, T. Hays and 84U Now*, William L. Etkins, Giulio D1Anzio, Robert H. 843 W .E. Hathaway, The Children's Hospital & University Glew, Lydia ii%iels,%iv. Pa. Sch. Med., Children's Hosp. of of Colorado Health Sciences Center, Denver, CO. Phila., Deut. of Ped., Univ. Pittsburgh Sch. Med., Dept. Biochem. , defined as an absolute neutrophil count 11000, A 19 year-old female with non-neuronopathic Gaucher's Disease occurs frequently in the general pediatric population. Its had 3 BMT's from 2 partially HLA-matched, carrier, sibling do- incidence and association with infection, both self-limited and nors. Pre-BMT glucocerebrosidase (glc-ase) activity in leuko- more serious, have not been well described. cytes and liver were 13 and 9% of controls respectively. BMT 81 A retrospective review of 1198 inpatients and 215 out- was done in 8/81 (donor=brother) after fractionated total lymph- patients was performed to determine the incidence. Three oid irradiation (100 rad x 18). Donor leukocytes (XY) were found percent of inpatients were found to have neutropenia. How- in the blood (1-3%) for 6 weeks and in marrow (6-9%) for 3 months ever, 80% of the children presenting with neutropenia were with no graft vs. host disease. A 2nd BMT (same donor) failed without signs or symptoms of infection. Three children had and graft cells disappeared. Leukocyte glc-ase activity never associated viral symptoms, 1 had a documented bacterial menin- changed. During 1982 the patient developed marrow failure. In gitis and 2 had a combination of viral and bacterial infection. 2/83, using a sister as donor, she had a 3rd BMT after cyclophos- The largest single diagnosis associated with neutropenia was phamide (120 mg/kg), total body x-ray (165 rad x 8) and cyclo- serous (SOM), accounting for 35% of neutropenia sporine. She engrafted promptly and had normal or supranormal inpatients. While making up only 35% of total admissions, 7.5% leukocyte glc-ase levels by day +27 and thereafter. At death on of all patients with the diagnosis of SOM had neutropenia. day +50 from cyclosporine toxicity ("capillary leak syndrome") Of 215 outpatients reviewed, 7% were neutropenic. As with and polymicrobial sepsis, her bone marrow showed partial clearing the inpatient group, a majority of children with neutropenia of Gaucher cells. Her liver had increased its glc-ase levels were without of infection. from 1.7 to 4.7 U/mg protein HI-glucocerebroside substrate; Neutropenia appears to be a common incidental finding in 25% normal). The brain had very low enzyme levels (12% normal). otherwise healthy children. In our study. it was most commonly Conclusion: BMT offers the Gaucher patient effective enzyme re- seen with serous otitis media. We conclude that neutropenia placement for cells of marrow origin in the circulation and in represented by the patients reviewed here is most likely short- reticuloendothelial organs. Whether remissions of clinical dis- lived, transient in nature, and needs no special evaluation or ease will occur and glc-ase levels in the CNS will rise after altered treatment plan, unless persistent or recurrent. BMT remains to he determined.

BILIRUBIN ALBUMIN BINDING (BAB) ASSAY IN PLATELET ASSOCIATED IMMUNE GLOBULIN(PAI~)INTHE 841 NEWBORN INFANTS BEFORE, DURING AND AFTER 844 COURSE OF CHILDHOOD IDIOPATH I c THROMBOCYTOPENI c EXTRACORPOREAL MEMBRANE OXYGENATION PURPURA.A.K.Brown,N.Gowda,S.MiIler,S.P.Rao&P.McFalI; (ECMO). Raul C. Banegale, Cindy Nixon, John Toomasian, Alice Andrews, Dietrich W. Roloff, and Robert H. Bartlett. (Spon. by W. F. Howett) Platelet associated immune globulin'was stbdied during the Depts. of Peds end Surg, Univ. of Michigan, Ann Arbor, ML course of ITP in 15 children; the microtiter solid phase immuno- Red blood cell destruction durine ECMO mav increase the risk for assay was used.Values in 10 patients with acute ITP were compar- hyperbilirubinemia and bilirubin nleurotoxicity." For this reason we ed with those in 5 children with chronic ITP. performed bilirubin binding studies on 12 newborn infants (mean t SD, At the onset,PAlgG was elevated in 9/10 children with acute gestational age 37.6t3.8 wks, birth wt 2889+706 gms) managed with ITP;~/~Ohad leveIs>70fg/pl (median PAlgG=91 .7;normal=<5.2fg/pl) ECMO for respiratory failure. The mean duration of ECMO was 91.1k37.2 The one child with acute ITP whose PAlgG was normal recovered hrs. Bilirubin binding studies including reserve bilirubin binding capacity within two weeks.At recovery PAlgG levels had fallen below (RBBC), and saturation index (SI) were performed using a bilirubin IOfg/pl(median 3.7 fg/pl) in 7/8;5/7 had normal levels. fluorometer. In contrast, 4/5 children whose disease became chronic, had No significant changes pre, on, or post ECMO were noted on the lower levels of PAlgG (<16.7fg/p1).0nly 1/5 chronic ITP patients hemoglobin and fibrinogen levels. The bilirubin levels were not had markedly elevated PA1gG.ln 2 patients post-splenectorny, significantly different pre and on ECMO and were lower post ECMO. levels were normal even in transient periods of thrombocytopenia As shown in the table, there were significant changes pre, on, and post In one patient,PAlgG rose dramatically to 75 fg/pl during an ECMO plasma hemoglobin values. Significant changes between pre and intercurrent viral illness. Another patient's PAlgG levels rose on ECMO values only were noted on the infant's platelet, fibrin split transiently following treatment with IV gamma globulin; no products and SGOT levels. Thus, the hemolysis that occurs during ECMO change in the platelet count occurred. does not adversely effect the RBBC and SI from any alterations in the These findings suggest that PAlgG is usually higher at the P,.... P~.C.~~,. r,..,. SCOT "0.. SL bilirubin load or in the onset of classic childhood ITP (acute) than in those children Xl.Wl*>" ~~lO~,.rn~, P,Dd""ll il"lL, ,mgi.ll ,rnS,6,, lypirnl, BAB sites. ECMO would whose course becomes chronic although the levels are not PRB BCIO 11.7.72 11011.65, 10211.2 II8.i.t ll.4.10 1P.I.1 individually predictive. The observed drop in PAlgG after 0",nil$, ICIO 0 3.21.1 I08 l-28 1 a1 3.190 71.1-1111) 16.512.1 3111.1 not predispose an infant ("~l2, splenectomy as well as the sharp rises noted during infection P EMP to bilirubin neurotoxicity ,"ilOj and gammaglobulin treatment deserve further study to help un- ce < 0, 0, " nsn because of the norma' 'Sil"l1rcanl. .#I repe.ld mearura derstand the relationship between thrornbocytopenia and PAIgG. ISi~".llcanl WCWeen me an0 on BCMO on$ BAB values pre, on, and *5.. *a, s,s"l,,r.nl. .ti rC0e.M mn.ui.r post ECMO.

INTRAVENOUS (IV) IMMUNOGLOBULIN G (IgG) THERAPY IN IMPAIRED SPLENIC RETICULOENDOTHELIAL FUNCTION IN CHILDHOOD NEUTROPENIA. Victor S. Blanchette and Jf 845 CHILDREN WITH . George R. Buchanan, Christine 842 Melvin H. Freedman. The Hospital for Sick Children, A Holtkam . Dept. of e iatrics, Univ. o exas Department of Pediatrics, Toronto, Canada. Health ~ciencdatDallas, SoLtdhwestern Medical LhoTol d High-dose IV IgG therapy may cause a rapid increment in plate- Children's Medical Center, Dallas. TX. let counts in children with immune thrombocytopenia. We have The reticuloendothelial (RE). phagocytic function of the evaluated this therapeutic approach in three children (2F, 1M: spleen is a major mechanism of defense aqainst invasive ages 10,22 and 30 mos.) with neutropenia and absolute neutrophil infections due to S: {n,eumoniae and H. influenza;, two organisms counts (ANC's) <500/ul. Patients were given 1 G/Kg of Sando- which often affect c 1 dren wlth cancer. Little information is globulin intravenously on each of two consecutive days. Two available about the effects of malianancv and of cvtntoxic-,---- - children had clear evidence of autoimmune neutropenia as evidenced agents on phagocytic function. he ref ope, studied splenic RE by: a) +ve circulating neutrophil (NAb): and b) normal function in children with cancer receiving diverse forms of in-vitro granulopoiesis (CFU-C) which was inhibited (50%( ) by chemotherapy by quantitation of pitted or pocked erythrocytes autologous serum. Both children had rapid responses to IV IgG (pit counts). The pit count (PC) is the percentage of therapy with ANC's increasing from 220 and 3601111 pre-therapy to erythrocytes containing one or more membrane-bound vesicles as 3110 and 53601~148 hrs. post-therapy. Responses were maintained determined by interference phase microscopy. The mean PC in 77 for 2 to 3 weeks. In one child impaired clearance of autologous, normal children and adults was 0.53% (range 0-2.0%), with only anti-D coated, 9ym~c-taggedred blood cells confirmed reticulo- 2.6% of normal subjects having values over 1.5%. Mean PC in 28 endothelial cell blockade as the mechanism of action of IV IgG. splenectomized subjects was 37% (range 3.2-81%). Among 158 As a control we treated one child with an inherited (autosomal children with cancer (361 specimens), the mean PC was 1.10% dominant) neutropenia. No response to IV IgG occurred. In this (range 0-12.6%). Forty-six patients (30%) had one or more values child neutropenia was due to impaired granulopoiesis with in-vivo above 1.5%, and 16 children (11%) had PC measurements above and in-vitro growth arrest at the myelocyte stage. Autologous 3.0%, a level previously suggested to have clinical sera had no effect on in-vitro cell growth (CFU-C) andcirculating significance. Elevated PC (> 1.5%) occurred in over 1/3 of NAb's were not present. These results suggest that high-dose IV children with Wilms' tumor and ALL and appeared to be related to IgG is a useful therapeutic option in patients with immune- chemotherapy rather than to the malignancy itself. Mild splenic mediated neutropenia; in-vitro studies of hematopoiesis and a RE hypofunction occurs in many children with cancer, probably search for circulating NAb's may predict those patients most results from chemotherapy, and may contribute to the risk of likely to respond to this therapeutic intervention. serious infection during treatment with cytotoxic agents.