Thalassemia among Chinese-Bostonians. Usefulness of the hemoglobin H preparation.

Microcytosis was noted in 14.7% of the complete blood cell count reports of Chinese subjects in a Boston Chinatown health center. One hundred forty-nine of these subjects' conditions were further evaluated by hemoglobin electrophoresis, Hb H inclusion bodies preparation, Hb A2 quantitation, and ferritin assay. Ninety-one cases of alpha-thalassemia-1 trait and 49 cases of beta-thalassemia trait were diagnosed. In this study population, the prevalence of thalassemia trait and of iron deficiency resulting in microcytosis was 13.8% and 3.4%, respectively. The Hb H preparation was found to be clinically useful and reliable for detecting alpha-thalassemia-1 trait in Chinese carriers, after the exclusion of iron deficiency and beta-thalassemia by routine studies.

Acute nonlymphoid leukemia.

Acute nonlymphoid leukemia (ANLL) is not an uncommon form of leukemia in children. The differential diagnosis is sometimes difficult, but there are a number of laboratory tests that can contribute useful information. Despite the introduction of several newer chemotherapeutic agents, only 50 to 60 percent of children with ANLL achieve complete remissions, and the median survival at this time is only about 14 to 18 months. Immunotherapy and bone-marrow transplantation may offer important future avenues of therapy. CNS leukemia has recently evolved as an important complication in this group of leukemias.

Immunochemotherapy in advanced neuroblastoma.

Twenty-two children with advanced (Stage III and IV) neuroblastoma have been treated in a nonrandomized fashion, half with a three-drug regimen consisting of vincristine, adriamycin, and cyclophosphamide, and half with this same drug combination plus the nonspecific immunostimulatory agent, MER/BCG. The addition of MER to the three-drug combination appeared to improve the duration of survival in this pilot study. The median duration of response was less than one year in the combination chemotherapy alone arm. The median duration of complete remission in children treated with the addition of MER has yet to be reached at 24 months.

Adjuvant treatment of osteogenic sarcoma with high-dose cyclophosphamide.

Six patients with osteosarcoma and no evidence of metastases received postoperative adjuvant chemotherapy with high-dose cyclophosphamide (25 mg/kg iv every other day for five doses). Three of these patients are alive without evidence of disease at 2 1/2, 3, and 5 years following diagnosis. The regimen was tolerable in terms of toxicity. Cyclophosphamide in high doses may be effective adjuvant therapy in some patients with osteosarcoma.

Combined therapy of osteosarcoma: preoperative irradiation, surgery, and chemotherapy.

The rationale for prebiopsy and preoperative irradiation in a multimodal approach to treatment of osteosarcoma is presented. Six patients with osteosarcoma underwent preoperative irradiation, amputation, and elective chemotherapy. Five of these also received prebiopsy irradiation: three survive without metastases at 29, 36, and 56 months, with no therapy for 10, 16, and 37 months, respectively; two patients died at 6 and 19 months of pulmonary metastases which appeared at 2 and 10 months, respectively. The latter two did not receive prebiopsy irradiation. Another patient, whose pulmonary metastasis regressed at 6 months with adriamycin and was later resected, died of cardiac failure at 59 months without evident metastasis. Immunologic aspects of the disease are also discussed.

Scene segmentation techniques for the analysis of routine bone marrow smears from acute lymphoblastic leukemia patients.

Automated analysis of lymphoblast cell morphology is being evaluated as a basis for predicting the response to therapy of patients with acute lymphoblastic leukemia. A new technique of scene segmentation particularly applicable to the "cluttered" images of cells in routine bone marrow smears is described. Morphologic characteristics of lymphoblasts found in bone marrow smears made at time of diagnosis were measured by an automated, interactive image-processing system using the new scene segmentation technique. These characteristics, on a patient by patient basis, are being compared to remission length and survival data to develop and test new prognostic methods.

The computer-assisted morphological classification of acute leukemia. I. Preliminary results.

The morphology of leukemic lymphoblasts, as seen in the initial routine bone marrow aspirate, of 40 children with ALL has been evaluated using a computer-assisted automated microscope. A statistic, derived from a combination of the number of macrolymphoblasts and the percentage of cells with no cytoplasm was found to predict response to standard therapy and to identify patients with a high probability of long-term remission as well as a group with a relatively poor response to therapy.

The role of haemolysis in neonatal hyperbilirubinaemia as reflected in carboxyhaemoglobin levels.

Carboxyhaemoglobin levels were measured in 250 consecutive, normal, term newborns and in a group of 75 severely jaundiced infants in an effort to assess the role of haemolysis in non-specific neonatal hyperbilirubinaemia--"Physiologic jaundice"-as well as in severe jaundice of various etiologies. In normal newborns a significant correlation (r=0.3293, p less than 0.001) was found between third-day carboxyhaemoglobin and serum bilirubin levels. Significant correlations were also found between the cord and third day values for carboxyhaemoglobin (infants of non-smoking mothers) for reticulocyte count, and for serum bilirubin. Third day haemoglobin showed no correlation with any of the other parameters including cord haemoglobin. Of the infants with third day carboxyhaemoglobin up to 0.75%, 1.7% had third day serum bilirubin values above 16.0 mg/100 ml. The corresponding percentage for the infants with carboxyhaemoglobin above 0.75% was 6.1%. It is concluded that increased rates of haemolysis due to as yet unspecified caused play an important role in the non-specific hyperbilirubinaemia of normal term newborns. As expected, high levels of carboxyhaemoglobin were found in infants with severe jaundice due to Rhesus and ABO haemolytic disease and glucose-6-phosphate dehydrogenase deficiency but also in jaundiced prematures and in Greek infants with severe jaundice of unknown cause.

Comparison of methodologies for thalassemia screening by Hb A2 quantitation.

An efficient, reliable, inexpensive screening test for beta-thalassemia triat is required before the National Cooley's Anemia Control Act can be carried out. Densitometry of hemoglobin samples separated by cellulose acetate has become a routine procedure to quantitate Hb A2 and thereby indicate beta-thalassemia trait carriers. To determine the utility of densitometry in quantitation of Hb A2, we evaluated three densitometers marketed in the United States. Individuals with genetically proved beta-thalassemia trait and normal Hb AA controls were studied. Two analytic procedures (elution and column chromatography) for Hb A2 quantitation were used as reference methods. Densitometry was shown to be unsatisfactory for detecting beta-thalassemia-trait carriers. We recommend that a unified approach to the detection of anemia, which would include thalassemia trait, be developed in the United States rather than free-standing thalassemia screening centers and clinics.