Phaedon Fessas

Patterns of bone marrow involvement in chronic lymphocytic leukemia and small lymphocytic (well differentiated) non-hodgkin's lymphoma. Its clinical significance in relation to their differential diagnosis and prognosis

Forty‐eight patients with chronic lymphocytic leukemia (CLL), and 12 patients with small (well differentiated) lymphocytic lymphoma (WDL) were histologically evaluated for their pattern of bone marrow (BM) involvement. Four different types of BM infiltration were recognized: nodular (N), interstitial (I), nodular and interstitial (mixed) and diffuse (D). The pattern of BM involvement was compared with the clinical, laboratory, and survival status in all patients. The extent of the disease in CLL patients, was determined by the Rai and the International Workshop on CLL Staging Systems, while in WDL patients the Ann Arbor staging system was used. In the CLL group the N pattern was found in 8%, the I in 33%, the mixed in 31%, and the D in 27% of the patients. Based on the International Workshop on CLL Staging System, the I pattern of BM involvement was more frequently found in Stage A (56%), the mixed in Stage B (68%), and the D in Stage C disease (90%). All CLL patients with D pattern required treatment from the beginning, contrary to CLL patients with the other patterns, in whom therapy was required in less than 50%. Similarly, deaths were more common in the D pattern than in the other patterns. In the WDL patients BM involvement was found in 4 of 12, (33%) and its pattern of positivity was always nodular, although most patients (10 of 12) had advanced disease. It is concluded that the frequency of BM involvement may contribute in the differential diagnosis of WDL from CLL. In addition, the pattern of BM infiltration correlates very well with the International Staging System for CLL, and the pattern of BM positivity in CLL patients also has prognostic significance.

B-chronic lymphocytic leukemia. Prognostic implication of bone marrow histology in 120 patients experience from a single hematology unit

The available staging systems for B‐chronic lymphocytic leukemia (B‐CLL) do not always predict the clinical course and the prognosis of the disease. In these systems, the pattern of bone marrow histology is not incorporated. In the current report we investigate the prognostic value of the diffuse or nondiffuse pattern of bone marrow involvement in 120 B‐CLL patients in relation to their actuarial survival, and we compare these results with the actuarial survival based on the International Workshop system. In addition, we analyze the influence of the diffuse or nondiffuse pattern on the actuarial survival, in relation to the individual clinical stages (A, B, C). All patients were diagnosed and followed‐up in the same Unit. Our patients were divided into Stage A (64), Stage B (22), and Stage C (34). They were also subdivided into those with a diffuse (46) and those with a nondiffuse (74) pattern of bone marrow histology. The difference in the actuarial survival in relation to their clinical stage (A, B, C) was statistically significant (P < 0.025). A greater statistical difference (P < 0.005) was found when the actuarial survival was analyzed in relation to the diffuse or nondiffuse pattern of bone marrow histology. No statistically significant differences could be found (P > 0.1), when the actuarial survival was calculated in every stage (A, B, C), on the basis of the diffuse or nondiffuse pattern of bone marrow histology. When our Stage A and B patients were analyzed for disease progression, in relation to the diffuse or nondiffuse bone marrow histology, it was found that 66.6% of the diffuse Stage A patients and 88% of the diffuse Stage B patients had disease progression as compared to only 8.6% for the nondiffuse Stage A patients and 33% for the nondiffuse Stage B patients. Our findings indicate that: the pattern of bone marrow histology in B‐CLL patients is the single most important prognostic parameter in this disease; a clinicopathologic staging system for B‐CLL may be justified; and the diffuse pattern of bone marrow histology could be considered as the best criterion for initiation of therapy in these patients. Cancer 59:767‐771, 1987.

Alpha-Chain of Human Hemoglobin: Occurrence in vivo

A minor hemoglobin component, apparently representing uncombined α-chains has been detected in the hemolysates of persons with inherited β-chain deficiency of moderate or severe degree. This finding supports the hypothesis that there is independent control of the synthesis of α-chains.

Angio-immunoblastic lymphadenopathy terminating as Hodgkin's disease.

The clinical course of a 33‐year‐old man with generalized lymphadenopathy bearing all physical, laboratory and histologic characteristics of “angio‐immunoblastic lymphadenopathy with dysproteinemia” (AILD) is described. Therapy was without significant benefit and the patient died 22 months after initial diagnosis. At autopsy in addition to the characteristic cellular polymorphism of AILD, numerous Hodgkins cells and Sternberg‐Reed cells were identified in the lymph nodes and spleen. Pleomorphic cellular infiltrates containing an increased number of immunoblasts and some giant cells were found also in the portal spaces of the liver. The evolution of Hodgkins disease (H.D.) from AILD suggests that the latter may have represented a reaction to the agent which causes H.D.

‘Silent’β-thalassaemia caused by a ‘silent’β-chain mutant: the pathogenesis of a syndrome of thalassaemia intermedia

In a Greek family three cases of β‐thalassaemia intermedia were diagnosed as resulting from the interaction of a typical high HbA2‐β‐thalassaemia with an atypical (silent) β‐thalassaemia gene. Following electrophoresis of globins on an acid‐urea‐Triton‐acrylamide system, an otherwise silent β‐like variant was revealed in the carriers of the atypical thalassaemia gene and in the intermediates; it amounted to 33% of the non‐α chains in the former and to c. 75% in the latter. The provisional name Hb Knossos is suggested for this abnormality.

A Unique Thalassaemic Syndrome: Homozygous α-Thalassaemia + Homozygous β-Thalassaemia

The disturbed balance of globin chain synthesis is a major factor in the pathophysiology of the thalassaemic disorders; this concept is strongly supported by the study of a patient displaying an extreme but symmetrical deficit of both major types of chains α and β. The patient had a mild clinical picture but presented a striking hypochromia (MCH 10 pg) with compensatory erythrocytosis (RBC 1012l.). Study of the propositus and his family by haematological, biochemical and biosynthetic techniques indicates that the patient carries two α‐ and two β‐thalassaemia genes resulting in balanced globin chain synthesis; in addition, several members of the family carry two or three abnormal genes. During observation a change in the haematological pattern occurred with a shift towards more intensive β‐chain and away from γ‐chain synthesis; this appeared with be associated with improvement of his anaemia through more effective erythropoiesis.

Monoclonal and Oligoclonal Immunoglobulins in the Serum of Patients with B-Chronic Lymphocytic Leukemia

The incidence of monoclonal and oligoclonal immunoglobulins (paraproteins) was determined in serum samples of 45 chronic lymphocytic leukemia (B-CLL) patients using the high-resolution agarose gel electrophoresis technique combined with immunofixation. Paraproteins were identified in 25 of the 45 patients tested. Twelve paraproteins were monoclonal and 13 oligoclonal. IgG kappa and/or lambda immunoglobulin isotypes were found in 17/25 of these patients. No correlation of the lymphocyte cell morphology and the presence of paraproteins was demonstrated. The high frequency of serum oligoclonal immunoglobulins in B-CLL indicates that more than one lymphocyte clone may be present in this disease.

Prevention of Thalassaemia and Haemoglobin S Syndromes in Greece

Clinically severe thalassaemia and Hb S syndromes are a major public health problem in Greece. A wide programme aiming at reducing the births of new cases is under way; it comprises (a) carrier identification either at a premarital stage or prior to the birth of first child and (b) prenatal diagnosis. Participation is voluntary and free of charge. Reduction of births of affected children has been obtained to a very large extent.

DISCUSSION PAPER PRENATAL DIAGNOSIS OF THALASSEMIA MAJOR IN GREECE: EVALUATION OF THE FIRST LARGE SERIES OF ATTEMPTS

The mean incidence of heterozygous , 3 thalassemia in Greece ranges between 3.3% and 14%.1-3 On the basis of this figure and the fact that the annual birth rate in this country is approximately 100,000 newborns, it is estimated that each year 800 couples risk giving birth to children with thalassemia major. Nowadays, information about this risk is spreading rapidly throughout the general population, and tests for the detection of carriers are easily available to young people through several programs. It is not surprising, therefore, that the ability to diagnose the severe form of the disease in utero *, has resulted in an exponentially increasing number of women seeking to have prenatal diagnosis rather than carrying a pregnancy at risk to term or having to resort to an abortion of a possibly unaffected child. Our group has been involved in prenatal diagnosis of thalassemia since the early steps of the procedure; the present paper summarizes our experience on the first 140 attempts. Technical aspects have been reported already and will not be repeated in detail here. The usual procedure is as follows: ( 1) Counseling of both partners about the chances and possibilities offered by the technique. (2) Localization of the placenta by ultrasound. If the placenta is considered to be accessible by the fetoscope no further measures are taken. Conversely, if it is foreseen that puncture of the placenta will create difficulties because of its position, the prospective mother is transfused with 4 units of packed red cells 10 days prior to the procedure. ( 3 ) In all experiments, a number of maternal erythrocytes equal to the number of cells obtained by the placental aspiration is processed in parallel with the fetal sample. (4) Separation of the globin chains is effected by chromatography on sodium carboxymethyl cellulose (CM-23) in urea-mercaptoethanol; the appropriate Na+ molarity gradient has been developed empirically using five chambers of a mixing apparatus.6 A typical example is shown in FIGURE 1. Analysis of the results is presented in the following TABLE 1.

IDENTIFICATION OF SLOW-MOVING HÆMOGLOBINS IN HÆMOGLOBIN H DISEASE FROM DIFFERENT RACIAL GROUPS

Abstract Slow-moving haemoglobin components have been found in small amounts in some patients with hœmoglobin H disease from Greece, Thailand, Malaysia, and Hong Kong. Chemical analysis indicates that in each case the abnormal haemoglobins are identical to haemoglobin Constant Spring (Hb CS), a variant with an elongated α-chain.