Klinefeiter's Syndrome, LSD Usage and Acute Lymphoblastic Leukemia

Clinical Genetics 1974: 6:20-22

Klinefeiter's syndrome, LSD usage and acute lymphoblastic leukemia

KI-YoNo SOHN AND DAM R. Booos The University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, U.S.A.

A 19-year-old boy, with Klinefelter's syndrome and a history of LSD usage, developed acute lymphoblastic leukemia. The possibility is discussed that this was caused by cyto- genetic injuries subsequent to LSD exposure and the inherited chromosomal anomaly acting in concert.

Received 10 September 1973, accepted for publication 26 February 1974

The patient presented here had Klinefelter's palpable, 2 cm under the left costal margin, syndrome (KFS), a history of LSD usage penis was normal and both testicles were and developed acute lymphoblastic leukemia palpable in the scrotum but were small (ALL). It seems possible that an additive el- (1.5)< 2.5 cm). No gynecomastia, lymph- fect of chromosomal abnormalities and LSD adenopathy, sternal tenderness, hepatome- usage might lead to increased susceptibility galy or purpura were noted. to leukemogenic factors. The hematocrit was 20 %, WBC 13,000/ rams with lymphoblasts as the predominant cell and platelets were 48,000/mma; the Case Report bone marrow aspirate was consistent with A 19-year-old male (No. 800-02-6716) was ALL. Twenty-four h urinary 17-ketosteroids first admitted to the Presbyterian-University were 23 mg (normal 8-24) and urinary Hospital, Pittsburgh, on February 16, 1972, pituitary gonadotrophin was 3.3 units (nor- for treatment of acute leukemia. During the real 6-50). 3 months before admission, he had noted Vincristine and prednisone therapy were weakness, anorexia, a 30-40 lb. (13.5-18.0 given and he achieved a complete hemato- kg) weight loss, easy bruisability and pallor, logic remission, but relapsed repeatedly and Physical examination revealed normal died 18 months after diagnosis. vital signs, height of 187.5 cm and weight of Past history included mental retardation 69.7 kg. He was pale with a high palate, and poor school performance. Further, the diminished facial and body hair and clinod- patient stated that he had used both mari- actyly of the right hand. The spleen was juana and LSD for about 3 years. He esti-

This study was supported by a research grant (AM-14352) from the National Institute of Arthritis and Metabolic Diseases and by a Fellowship Grant to Dr. Sohn from the Leukemia Society of America. SOHN AND BOGGS 21

mated having been on several "trips" with elude that the frequency of leukemia is LSD, and last used it 6 months before ad- greater than that seen in the general pop- mission, ulation. However, cultures of fibroblasts Initial chromosome examination of blood from KFS patients show an increased fre- cells cultured with phytohemagglutinin quency of transformation when cultured revealed two extra C-group chromosomes in with SV 40 virus as compared to normal 18/20 metaphases and in some cells other cells (Mukerjee et al. 1970), a phenomenon chromosomes were missing, leading to a which might have predictive value for an variable degree of aneuploidy. During re- increased chance of developing cancer (Mil- mission, all cells examined contained two ler & Todaro 1969). A large scale survey xtra C-group chromosomes. Barr bodies of the frequency of leukemia and other were present in 20 of these 46 cells. Thus, malignancies in KFS would be of interest. the extra C-group chromosomes were as- LSD causes chromosome abnormalities sumed to be X-chromosomes and the patient similar to those observed with such leuke- was presumably a KFS of the XXXY mia predisposing agents as benzene and variety, ionizing radiation (Dishotsky et al. 1971) and at least three cases of leukemia have been reported in LSD users (Grossbard et Discussion al. 1968, Tylden 1968, Garson & Robson Although this association of KFS and LSD 1969). with acute lymphoblastic leukemia (ALL) In contrast to KSF, certain other dis- may be a chance phenomenon, the possi- orders associated with chromosome abnor- bility that leukemia was the result of the malities such as mongolism (Fraumini & cytogenetie abnormalities associated with Miller 1967) serve greatly to increase the KFS, or with LSD usage, or due to an ad- likelihood of malignancy. Certain pre- ditive effect of both conditions must be zygotic aberrations, including an abnormal considered, number of sex chromosomes, may also con- The present case represents at least the tribute to this tendency. For example, Bor- tenth report of the co-existence of this sex ges et al. (1967) reported that four of 25 -- chromosome abnormality and a hematologic non-mongoloid children with acute leukemia malignancy (Table 1). KFS occurs in ap- in remission had karyotypic abnormalities, proximately one in 500 males (Beeson & including 47 XXY, which developed prior McDermott 1971), so it is difficult to con- to conception.

Table 1 Reports of Klinefelter's syndrome and leukemia-lymphoma

Authors Karyotype Age in years Neoplasia

Augustine& Jaworski(1958) Unknown 52 Reticulumcell sarcoma MacSween(1965) XY/XXWXXXY 53 Reticulumcelt sarcoma Beckeret al. (1966) Unknown Unknown Lymphosarcoma Toughet al. (1961) XYIXXY 59 Chronicmyelocyticleukemia Fitzgeraldet al. (1971) XWXXY 69 Chronicmyelocyticleukemia Mamuneset al. (1961l XXY 36 Acutemyeloblasticleukemia Borgeset al. (1967) XXY 2-1/2 /_,cuteundifferentiatedleukemia Bousser& Tanzer(1963) XXY 32 Acutelymphoblas1'leukemiaic Ruffleet al. (1966) XXY Unknown Acutelymphoblasticleukemia Ki-YongSohn& eoggs (1974) XXXY 19 Acutelymphoblasticleukemia 22 SOHN AND BOGGS

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