Hematopoietic stem cell regulatory volumes as revealed in studies of the bgj/bgj:W/WV chimera.

The kinetics of bone marrow replacement was studied in W/WV mice implanted with gbj/bgj (beige) stem cells, with the characteristic beige neutrophil marker as a criterion of the takeover of host marrow by donor marrow. A hyperbolic pattern of W/WV marrow replacement conforming to a log dose-response was observed in experiments encompassing a 50-fold range of bgj/bgj inoculum doses and a 2-yr period of observation. The dose-response relationships were consistent with random seeding of stem cells in the host marrow coupled with a decreasing efficiency of secondary colonization by local migration. Application of single-hit Poisson sampling statistics to the dose-response data led to the hypothesis that mouse bone marrow is compartmentalized into essentially self-contained stem cell regulatory volumes or domains. We estimate that W/WV marrow contains about 2,600 stem cells regulatory units with an average volume of about 10(8) micron3, a dimension consistent with the presumptive role of short-range cell-cell interactions in the regulation of pluripotent stem cells. Our analysis of the dose-response data is also indicative of the discontinuous and limited nature of local stem cell migration in a cellular marrow, a consideration that may be of practical as well as theoretical interest.

Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine.

PURPOSE: To assess thiopurine S-methyltransferase (TPMT) phenotype and genotype in patients who were intolerant to treatment with mercaptopurine (MP) or azathioprine (AZA), and to evaluate their clinical management. PATIENTS AND METHODS: TPMT phenotype and thiopurine metabolism were assessed in all patients referred between 1994 and 1999 for evaluation of excessive toxicity while receiving MP or AZA. TPMT activity was measured by radiochemical analysis, TPMT genotype was determined by mutation-specific polymerase chain reaction restriction fragment length polymorphism analyses for the TPMT*2, *3A, *3B, and *3C alleles, and thiopurine metabolites were measured by high-performance liquid chromatography. RESULTS: Of 23 patients evaluated, six had TPMT deficiency (activity < 5 U/mL of packed RBCs [pRBCs]; homozygous mutant), nine had intermediate TPMT activity (5 to 13 U/mL of pRBCs; heterozygotes), and eight had high TPMT activity (> 13.5 U/mL of pRBCs; homozygous wildtype). The 65.2% frequency of TPMT-deficient and heterozygous individuals among these toxic patients is significantly greater than the expected 10% frequency in the general population (P <.001, chi(2)). TPMT phenotype and genotype were concordant in all TPMT-deficient and all homozygous-wildtype patients, whereas five patients with heterozygous phenotypes did not have a TPMT mutation detected. Before thiopurine dosage adjustments, TPMT-deficient patients experienced more frequent hospitalization, more platelet transfusions, and more missed doses of chemotherapy. Hematologic toxicity occurred in more than 90% of patients, whereas hepatotoxicity occurred in six patients (26%). Both patients who presented with only hepatic toxicity had a homozygous-wildtype TPMT phenotype. After adjustment of thiopurine dosages, the TPMT-deficient and heterozygous patients tolerated therapy without acute toxicity. CONCLUSION: There is a significant (> six-fold) overrepresentation of TPMT deficiency or heterozygosity among patients developing dose-limiting hematopoietic toxicity from therapy containing thiopurines. However, with appropriate dosage adjustments, TPMT-deficient and heterozygous patients can be treated with thiopurines, without acute dose-limiting toxicity.

Hydroxyurea therapy for diverse pediatric populations with sickle cell disease.

Hydroxyurea (HU) is the first widely used treatment to have an impact on the severity of disease in adult patients with sickle cell anemia, but limited data are available for younger patients or those with variant genotypes. We reviewed 324 months of experience with HU in 16 patients from 5.3 to 18.4 years of age treated for 6 to 50 months. The major toxicity was reversible neutropenia. Linear growth continued unchanged, and all patients gained weight. Hematologic results were similar to those reported in adults with increases in mean corpuscular volume (MCV) and total and fetal hemoglobin (HbF). We noted that the maximal hematologic effects occurred at less than the maximum dose. Clinically, patients experienced an 80% reduction in episodes of acute chest syndrome and a reduced need for blood transfusion, as well as a 30% decrease in the number of hospitalizations for painful events during HU therapy compared with an equivalent number of months before HU. These highly statistically significant results confirmed the value of HU in ameliorating the severe clinical course of pediatric patients. Similar effects were observed in three patients with sickle beta degrees-thalassemia, sickle beta+-thalassemia, and S-O Arab. Recurrent acute splenic sequestration and progressive symptomatic osteonecrosis were observed during HU. Thus, HU may not prevent the development of complications once organ damage is present. The challenge remains to determine when and to which pediatric patients with sickle cell disease HU should be offered.

Multisystem damage associated with tricorporal priapism in sickle cell disease.

PURPOSE: Priapism is an uncommon but debilitating complication of sickle cell disease (SCD). Recent observations among adult males regarding the abysmal failure of medical and surgical therapy encouraged us to review our 25-year experience identifying the prognostic features that might determine outcome. PATIENTS AND METHODS: As part of a prospective 25-year longitudinal demographic and clinical cohort study, a subset of 38 (8.2%) patients with priapism were identified among a cohort of 461 men with SCD. The patients with priapism were compared with the nonaffected men with respect to severity of disease expression, hematologic status, beta s globin gene haplotype, and the incidence of sickle-related major organ failure. The influence of the treatment modalities on outcome was also evaluated. RESULTS: Priapism occurred as a single episode in 24 patients, and in 14 as temporally clustered repeat episodes. Eighty-seven percent of those with priapism had sickle cell anemia (SS), an increased risk as compared with other variants of SCD (p = < 0.05). There were two distinct age-related patterns of disease expression. Eight patients were prepubertal; they experienced shorter episodes, involvement of the corpora cavernosa only, few recurrent episodes, and a good prognosis for future erectile function. Non-surgical therapy in children was associated with excellent results. In contrast, the 29 postpubertal adults often had involvement of the corpora cavernosa and corpus spongiosa (tricorporal disease) and half had prolonged episodes that lasted longer than 8 days. One pubescent patient had repeated episodes and became impotent. Prolonged or repeated episodes eventuated in impotence in 56%. Surgical intervention was not beneficial. Sickle cell-related organ failure such as stroke, chronic restrictive lung disease, chronic renal failure, and nonhealing leg ulcers was observed more frequently in men who had priapism. Death occurred in nine adult patients (25%) within 5 years of the first episode of priapism. CONCLUSION: Priapism in adult males identifies those at high risk for other sickle cell-related organ failure syndromes and, as such, is another complication indicative of severe disease. The dismal prognosis in SS adults requires better understanding of the precise pathophysiology of low-flow tricorporal priapism. Clarification of the mechanisms inducing the priapic state should lead to specific therapeutic maneuvers and an improved prognosis for this disabling condition.

Hematological abnormalities and cholestatic liver disease in two patients with mevalonate kinase deficiency.

We describe two patients with mevalonate kinase deficiency and prominent hematologic abnormalities and cholestatic liver disease. Patient R.B. was not anemic at birth, but developed petechiae and cutaneous extramedullary hematopoiesis, hepatosplenomegaly, leukocytosis, and recurrent febrile events without positive bacterial or viral cultures. Patient N.M. manifested minor anomalies, hepatosplenomegaly, anemia, thrombocytopenia, recurrent febrile crises, and facial rashes. Mevalonic aciduria was found by urinary organic acid analysis, and mevalonate kinase deficiency was documented in both. The clinical spectrum of normocytic hypoplastic anemia, leukocytosis, thrombocytopenia, and abnormal blood cell forms led to diagnoses of congenital infection, myelodysplastic syndromes, or chronic leukemia in these patients before recognition of mevalonate kinase deficiency. Mevalonate kinase deficiency represents a single-gene abnormality that may be associated with significant hematologic findings. Recognition of the variability of this disorder with some patients manifesting only mild neurologic findings, yet significant hepatosplenomegaly, normocytic anemia, thrombocytopenia, and leukocytosis is important for all specialists who need to be aware of this organic aciduria.

Polymerase chain reaction amplification of archival material for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis.

Bone marrow hemophagocytosis may occur as an incidental finding, or it may be a manifestation of a systemic and potentially lethal disorder. When systemic, the proliferation is termed hemophagocytic lymphohistiocytosis (HLH), a clinicopathologic entity characterized by a widespread proliferation of benign hemophagocytic histiocytes, fever, pancytopenia, deranged liver function, and frequently coagulopathy and hepatosplenomegaly. A variety of infectious agents, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19), have been associated with HLH, but the relative frequency of each using one technique has not been evaluated. In addition, infectious causes of incidental bone marrow hemophagocytosis, not occurring in the setting of HLH, have not been evaluated. Review of bone marrow reports from bone marrow examinations done between December 1986 and June 1997 showed that 20 children aged 2 months to 15 years had bone marrow examinations that indicated hemophagocytosis. Archival materials from 19 patients were successfully retrieved, and DNA was extracted from archived unstained coverslips with subsequent polymerase chain reaction for EBV, CMV, HHV6, and PVB19 genomic DNA. DNA extracted from 16 bone marrow specimens of age-matched children was used as negative controls. Eleven of the 19 patients fulfilled the clinical and pathological criteria for HLH; the remaining eight patients had isolated hemophagocytosis without a systemic presentation. Viral DNA was detected in 8 of 11 patients with HLH but in none of eight patients with isolated hemophagocytosis. EBV was present in five of the bone marrows, followed in frequency by HHV6, CMV, and PVB19. Infection with more than one agent was present in three patients. Only one control patient was positive for HHV6 DNA; the remaining control patients were negative for all viruses. Viral infection, detected by PCR analysis of bone marrow, is a common finding in patients with HLH but not in patients with isolated bone marrow hemophagocytosis. This technique may provide another marker to aid in the diagnosis of HLH and suggests a different cause of hemophagocytosis occurring in patients with and without HLH.

Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression.

Two patients with hematologic relapse of chronic myelogenous leukemia (CML) following allogeneic BMT were treated by abrupt discontinuation of cyclosporine. Both patients rapidly attained complete hematologic and cytogenetic remission and remain free of disease with long follow-up. In the first patient, disappearance of CML was associated with the development of graft-versus-host disease (GVHD). In the second patient GVHD did not develop until after clearing of disease had been documented by cytogenetic analysis. Laboratory studies in the second patient disclosed the presence of lytic activity against both K562 and autologous CML cells that enhanced with IL2. Correlation with serial immunophenotyping data from this patient suggests that the effector for this graft-versus-leukemia (GVL) reaction could have been a T lymphocyte. Abrupt discontinuation of post-transplant immunosuppression with cyclosporine may represent a therapeutic approach to CML which has recurred following BMT. Moreover, investigation of this clinical phenomenon in subsequent cases may permit direct study of the cellular mechanisms involved in the GVL effect.

Report of the American Foundation for Urologic Disease (AFUD) Thought Leader Panel for evaluation and treatment of priapism.

PURPOSE: Patients with priapism often develop permanent erectile dysfunction and personal sexual distress. This report is intended to help educate the public by reviewing the varied definitions and classifications of priapism and limited literature reports of pathophysiology, diagnosis and treatment outcomes of priapism. The AUA priapism guidelines committee is responsible for creating consensus as to appropriate individual patient management of priapism by physicians. MATERIALS AND METHODS: A multidisciplinary panel, consisting of 19 thought leaders in priapism, was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease to address pertinent issues concerning the role of the urologist, primary care providers and other health care professionals in the education of the public regarding management of men with priapism. The panel utilized a modified Delphi method and built upon the peer review literature on priapism. RESULTS: The Thought Leader Panel recommended adoption of the definition of priapism as a pathological condition of a penile erection that persists beyond or is unrelated to sexual stimulation. Priapism is stressed to be an important medical condition that requires evaluation and may require emergency management. The classification system is categorized into ischemic and non-ischemic priapism. Essential elements of the ischemic classification are the inclusion of: (i) clinical characteristics of pain and rigidity; (ii) diagnostic characteristics of absence of cavernosal arterial blood flow; (iii) pathophysiological characteristics of a closed compartment syndrome; (iv) a time limit of 4 h prior to emergent medical care; and (v) a description of the potential consequences of delayed treatment. Essential elements of the non-ischemic classification are the inclusion of: (i) clinical characteristics of absence of pain and presence of partial rigidity; (ii) diagnostic and pathophysiological characteristics of unregulated cavernosal arterial inflow; and (iii) the need for evaluation but emphasizing the lack of a medical emergency. The panel recommended adoption of a rational management algorithm for the assessment and treatment of priapism where the cornerstone of initial assessment includes a careful clinical history, a focused physical examination and selected laboratory and/or radiologic tests. The panel recommended that specific criteria and clinical profiles requiring specialist referral should be identified. The panel further recommended that patient (and partner) needs and education concerning priapism should be addressed prior to therapeutic intervention, however only in the case of chronic management or post acute presentation evaluation should this delay intervention. Treatment goals to be discussed include management of the priapism with concomitant prevention of permanent and irreversible erectile dysfunction and associated psychosocial consequences. The panel recommended that when specific therapies for priapism are required, a step-care treatment approach based upon reversibility and invasiveness should be followed. CONCLUSIONS: The Thought Leader Panel calls for research to expand our understanding of the prevalence and diagnosis of priapism and education to create awareness among the public of the potential urgency of this condition. Critical areas to be addressed include the multiple pathophysiologies of priapism as well as multi-institutional trials to objectively assess safety and efficacy in the various treatment modalities.

Hematologic findings in Southeast Asian immigrants with particular reference to hemoglobin E.

Recent immigrants from Southeast Asia were screened for hematologic abnormalities using a multichannel cell counter (Coulter S), peripheral smear, free erythrocyte protoporphyrin (FEP), isoelectric focusing, and a qualitative screen for glucose-6-phosphate dehydrogenase deficiency. Hematologic abnormalities were further defined by hemoglobin electrophoresis, globin electrophoresis, HbA2 levels, and HbF levels. Of the 189 adults studied, 68 (36 percent) were hematologically abnormal, including 28 hemoglobin E (HbE) heterozygotes, six HbE homozygotes, 14 with alpha-thalassemia minor, and 10 with presumptive iron deficiency. Of the 54 people with microcytic (MCV less than 80fl) red blood cells (RBC), 52 had evidence of HbE or thalassemia and two had iron deficiency alone; five had both iron deficiency and a hemoglobinopathy. Homozygosity for HbE results in an asymptomatic condition similar to thalassemia minor with microcytic RBC, large numbers of target cells, normal or slightly reduced hematocrit and greater than 90 percent HbE. People heterozygous for HbE are asymptomatic and have hematologic findings similar to thalassemia minor with slightly reduced or low normal MCV and 25 to 35 percent HbE.

Correlation of serum cholylglycine level with hepatic dysfunction in children with sickle cell anemia.

Hepatic dysfunction occurs commonly in children with sickle cell disease (SCD). Although the etiology is multifactorial, cholestasis is a prominent feature. Serum cholylglycine (CG) has been found to be a very sensitive indicator of cholestasis. Our objective was to determine whether CG levels are elevated in children with SCD and whether they are predictive of hepatic dysfunction. Blood samples were obtained from 97 children with SCD. Liver function tests were done and serum CG concentrations were measured. Patients were followed up for 2 years. Thirty-eight percent of the patients had an elevated CG level. During the 2 years of follow-up, 16% of the children with a previously elevated CG level developed abnormal liver function test results or required a cholecystectomy as compared with 13% with a previously normal CG level (p = 0.92). We conclude that although CG level was elevated in 38% of the patients with SCD, it did not appear to predict liver dysfunction during the ensuring 2 years.

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Bacteremia in children with sickle hemoglobin C disease and sickle beta(+)-thalassemia: is prophylactic penicillin necessary?

OBJECTIVE: To characterize the incidence of bacteremia and its potential for progression to septicemia in children with sickle hemoglobin C disease and sickle beta(+)-thalassemia to assess the need for penicillin prophylaxis. STUDY DESIGN: Retrospective chart review of the frequency and natural history of bloodstream infection in such patients not receiving prophylactic penicillin therapy and followed up in a single institution. RESULTS: During more than 842 patient-years of observation in 242 patients with sickle hemoglobin C disease, 15 episodes of bacteremia occurred in nine patients. Septicemia was fatal in one patient. The overall incidence of bacteremia, 1.8 events per 100 patient-years (95% confidence limits: 0.8, 2.8) in patients with sickle hemoglobin C disease, was similar to that in hematologically normal children. One episode of bacteremia occurred in a patient with sickle beta(+)-thalassemia. CONCLUSIONS: The incidence of bacteremia is not increased in young patients with sickle hemoglobin C disease and sickle beta(+)-thalassemia. Further, unlike its course in children with sickle cell anemia, it rarely evolves into life-threatening septicemia. This probably results from the maintenance of relatively intact splenic function during infancy and early childhood in patients with sickle hemoglobin C disease and sickle beta(+)-thalassemia. Prophylactic penicillin therapy may not be required in these patients.

Polymerase chain reaction amplification of archival material for parvovirus B19 in children with transient erythroblastopenia of childhood.

The relationship between transient erythroblastopenia of childhood (TEC) and parvovirus B19 infection remains uncertain. Large series using primarily serologic evaluation have not shown an association, whereas smaller series have reported parvovirus B19 infection in such patients. Further, parvovirus DNA or antigen has been detected in some patients seronegative for the virus at presentation. Polymerase chain reaction (PCR) amplification has never been used to evaluate patients with TEC for parvovirus B19. We used the PCR in an attempt to detect parvovirus B19 in DNA extracted from archived bone marrow coverslips of 16 patients diagnosed with TEC. The patients ranged in age from 3 to 23 months and presented with a mean hemoglobin value of 5.4 g/dL. Sixty-nine percent were neutropenic and none was thrombocytopenic. None of the patients had histologic evidence of parvovirus B19 infection in the bone marrow. DNA amplification for parvovirus B19 was negative in each case. In contrast, parvovirus B19DNA was amplified from DNA isolated from archived bone marrow coverslips of a patient with known parvovirus B19 infection, indicating that the PCR assay was sufficiently sensitive to detect virus from archieved bone marrow coverslips. Review of the literature indicates that the patients with parvovirus-associated TEC are generally older and often present with concomitant thrombocytopenia, whereas patients with parvovirus B19-negative TEC are younger and present without thrombocytopenia, similar to the patients in our study. Our results suggest that parvovirus B19 is not the cause of anemia in the young patient with typical features of TEC. Rather, parvovirus B19 infection of older, previously healthy children may occasionally cause a protracted anemia, often with thrombocytopenia, which may be diagnosed by some as TEC.

Laparoscopic splenectomy in childhood hematologic disorders.

Laparoscopic splenectomy is a new technique that is being utilized in patients with a variety of mostly hematologic disorders. Its application in children has not been extensively documented. Between January 1994 and February 1995, 11 children less than 15 years of age underwent elective laparoscopic splenectomy. Data collected from this treatment group were compared to that from the ten most recent open splenectomy patients with comparable hematologic disorders. All procedures in both groups were successful in relief of symptoms, increase in platelet count, and/or increase in hematocrit. Operative times averaged 147 mm in the laparoscopic group, compared to 112 mm in the open group. Estimated blood loss was 32 ml in the laparoscopic group and 86 ml in the open group. Days to laparoscopic patient discharge were 3.6, compared to 5.3 days in the open group. There were no wound complications or need for perioperative platelet transfusions in the laparoscopic patients. Patient response has been uniformly positive in the laparoscopic group. Reusable access trocars are utilized for two of the four working ports. Stapling devices and special tissue morselizers are not required. There are no additional operating room or surgeons fees incurred in the laparoscopic procedures. This series demonstrates that laparoscopic splenectomy is a safe, cost-efficient alternative to open splenectomy in children with a variety of hematologic disorders.

Prevalence of priapism in children and adolescents with sickle cell anemia.

A questionnaire survey was conducted of patients with homozygous sickle cell anemia (Hb SS) and sickle cell beta(0)-thalassemia (Hb S-beta(0)) between 5 and 20 years of age to determine the prevalence and characteristics (number of episodes, timing, duration, cause, or precipitating event) of priapism. Ninety-eight male patients or their parents were surveyed by the same male investigator using a structured verbal interview, which was modified according to the age of the patient. Ninety-four patients had Hb SS and four Hb S-beta(0) thalassemia. Eleven (11%) patients were known to have experienced priapism previously. In response to the questionnaire, 16 of the remaining 87 (18%) patients reported having had priapism on one or more occasions. The actuarial probability of experiencing priapism by 20 years of age was 89% (+/- 9%). The mean age at the initial episode was 12 years, the mean number of episodes per patient was 15.7 (median, 1; range, 1-100), and the mean duration of an episode was 125 minutes. Episodes typically occurred around 4:00 am, and 75% of the patients surveyed had at least one episode starting during sleep or upon awakening from sleep. The prevalence of priapism in children and adolescents with SCA is much higher than previously described. Since early intervention and treatment may prevent irreversible penile fibrosis and impotence, patients and parents should be educated about this complication in advance of its occurrence.

Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.

The optimal management of prolonged priapism for patients with sickle cell anemia (SCA) has not been established. We prospectively studied in an outpatient setting the efficacy and safety of a procedure that employs aspiration of blood from the corpora cavernosa and irrigation with a dilute epinephrine solution under local anesthesia to relieve priapism in young patients with SCA. If hydration and analgesics failed to produce detumescence or if priapism had lasted >4 hours, the protocol was activated in the emergency room or clinic. Fifteen patients with homozygous SCA (Hb SS) were treated on 39 occasions; 10 patients were treated once, 1 patient twice, 2 patients 3 times, 1 patient 6 times, and 1 patient 15 times. Median age of patients at first treatment was 14.3 years (range, 3.9-18.3 years). The procedure was successful in producing immediate detumescence on 37 of 39 occasions (95% efficacy, 95% confidence intervals (CI): 81%-99%). No serious immediate or long-term side effects were observed. None of the patients who demonstrated detumescence required hospitalization. The 2 patients whose priapism persisted after aspiration and irrigation presented with episodes lasting >24 hours. All evaluable patients whose priapism resolved after aspiration and irrigation self-reported normal erectile function at a median of 40 months (range, 3-58 months) after the last procedure. Thus, aspiration of the corpora cavernosa followed by irrigation with dilute epinephrine is effective in producing immediate and sustained detumescence and should be the initial therapy employed for patients with SCA and prolonged priapism. (Blood, 2000; 95:78-82)

A two-year pilot trial of hydroxyurea in very young children with sickle-cell anemia.

OBJECTIVE: Hydroxyurea improves hematologic values and decreases vaso-occlusive complications in adults and children with sickle cell anemia (SCA), but has not been tested in infants before the onset of chronic organ dysfunction. We conducted a collaborative pilot trial of hydroxyurea in infants with SCA to assess its (1) feasibility of administration, (2) toxicity, (3) hematologic effects, and (4) effect on spleen function. STUDY DESIGN: Patients with hemoglobin (Hb) SS or Sbeta(0) thalassemia (n = 28, median age 15 months) received hydroxyurea for 2 years at 20 mg/kg/day. Hydroxyurea was temporarily discontinued for predefined toxicity. RESULTS: Seven patients exited the study early: five for noncompliance or refusal to continue, one for mild stroke, and one for fatal splenic sequestration. The predominant toxicity was transient neutropenia, which was usually associated with a viral-like illness. After 2 years of treatment, mean Hb level = 8.8 g/dL and Hb F = 20.3%, both higher than predicted age-specific levels. Radionuclide splenic uptake was absent in 47% of patients at study completion, compared with predicted functional asplenia in 80% of the patients. CONCLUSIONS: Hydroxyurea therapy for infants with SCA is feasible and well tolerated, has hematologic efficacy, and may delay functional asplenia. The potential for hydroxyurea to preserve organ function in SCA should be further evaluated.

Comparison of laparoscopic and open splenectomy in children with hematologic disorders.

OBJECTIVE: To compare laparoscopic and traditional open splenectomy in children with nonmalignant hematologic disorders. STUDY DESIGN: Retrospective review of 36 consecutive nonrandomized splenectomies (16 laparoscopic and 20 open) performed for hematologic disorders at a single pediatric institution during the past 3 years. The two-sided Mann-Whitney U test for non-parametric variables was used for statistical analysis. RESULTS: An open procedure was performed on 20 patients (mean age, 9.7 years), five of whom had a concomitant cholecystectomy. A laparoscopic splenectomy was performed on 16 children (mean age, 10.3 years), seven of whom had a concomitant cholecystectomy. The mean anesthesia and operative times were longer in the laparoscopic than in the open group (p < 0.001). However, the mean number of hours of postoperative analgesia was less in the laparoscopic group (p < 0.005). Patients who had laparoscopic splenectomy were also discharged home earlier (p < 0.01) and resumed a regular diet sooner. Mean operating room charges were higher in the laparoscopic group (p < 0.001), but total hospitalization costs were not significantly different. Postoperative complication rates were similar. The hematologic response was comparable. CONCLUSIONS: laparoscopic splenectomy is feasible and safe in children with hematologic disorders. Although it currently requires more operative time than the open approach, it is superior with regard to duration of postoperative analgesia, duration of hospital stay, and recovery of bowel function.

Nonblack patients with sickle cell disease have African beta S gene cluster haplotypes.

Of 18 nonblack patients with sickle cell disease, 14 had sickle cell anemia, 2 had hemoglobin SC disease, and 2 had hemoglobin S-beta o-thalassemia. The beta s gene cluster haplotypes that were determined in 7 patients were of African origin and were identified as Central African Republic, Central African Republic minor II, Benin, and Senegal. The haplotype Central African Republic minor II was present on the beta o-thalassemia chromosome in 2 patients. None of 10 patients whose alpha-gene status was determined had alpha-thalassemia-2. These data strongly support the concept that the beta s gene on chromosome 11 of these individuals is of African origin and that the alpha-gene locus on chromosome 16 is of white or native American origin. The clinical severity of the disease in these nonblack patients is appropriate to their haplotype without alpha-thalassemia-2 and is comparable with that of black patients. All persons with congenital hemolytic anemia should be examined for the presence of sickle cell disease regardless of physical appearance or ethnic background.