leukemia in newborn infants with down syndrome

1
Leukemia Research Vol. 17, No. 2, p. 195, 1993. 0145-2126/93 $6.00 + .00 Printed in Great Britain. © 1993 Pergammon Press Ltd LETTER TO THE EDITORS LEUKEMIA IN NEWBORN INFANTS WITH DOWN SYNDROME (Received 6 August 1992. Accepted 22 August 1992) THE LETTERfrom Dr K. Ghosh, entitled "Transient abnormal myelopoiesis in Down syndrome--are some of them truly leukemia?", published in Leu- kemia Research, 16, 545 (1992) was of great interest to us. There are several features of the case which are unique and different from previously published cases of transient abnormal myelopoiesis or transient leukemia in Down syndrome [1]. The first is the very high count of blasts in the peripheral blood (209 × 109/0, the second is the high percentage of blasts in the bone marrow (95%), and the third is the presence of monosomy 7 in blood cells. The presence of monosomy 7, a clonal population, was interpreted by Dr Ghosh as evidence that tran- sient leukemia in Down syndrome is leukemia. Although cytogenetic abnormalities are not common in transient leukemia they do occur and in addition to the case described in Dr Ghosh's letter and one report cited therein we have seen one case of tran- sient leukemia with tetrasomy 21 and one in which the karyotype of the leukemic cells was 47xy + 21 der(5) t(1; 5) (q25; q32). There have been other reports of chromosomal abnormalities in the leu- kemic cells of transient leukemia including pen- tasomy 21 [2] and an x-8 translocation [3]. Also one case has been reported [4] in which an additional C chromosome was found in the leukemic cells at birth; the patient developed acute megakaryoblastic leu- kemia several years later at which time the initial chromosomal abnormality re-appeared. We support Dr Ghosh's speculation that transient leukemia may be leukemia. In addition to the cyto- genetic data cited above we believe there is sub- stantial evidence to support this thesis: 1. The cells in the blood have been identified as megakaryoblasts [5]. 2. The proliferation of megakaryoblasts in transient leukemia is clonal [6]. 3. In approximately 20% of cases, acute mega- karyoblastic leukemia will develop [1]. 4. In some cases, the disease is fatal or life threat- ening due to hydrops and/or congestive heart fail- ure [7]. 5. In fatal cases, postmortem studies reveal leukemic infiltration with or without fibrosis in liver and other tissues [8]. We conclude therefore that transient leukemia in Down syndrome is leukemia that usually disappears spontaneously but may be persistent or fatal, and may recur as acute megakaryoblastic leukemia. REFERENCES 1. Zipursky A., Poon A. & Doyle J (1992) Leukemia in Down Syndrome: a review. Pediat. Hemat. Oncol. 9, 139. 2. Rogers P. C. J., Thomas J. W. & Kalousek D. K. et al. (1983) Neonate with Down's Syndrome and transient congenital leukemia. Am. J. Ped. Hem./Onc. 5, 59. 3. Lazarus K. H., Heerema N. A. & Palmer C. G. et al. (1981) The myeloproliferative reaction in a child with Down Syndrome: cytological and chromosomal evi- dence for a transient leukemia. Am. J. Hemat. 11,417. 4. Honda F., Punnett H. H. & Charney E. et al. (1964) Serial cytogenetic and hematologic studies on a mongol with trisomy 21 and acute congenital leukemia. J. Pediat. 65, 880. 5. Coulombel L., Derycke M. & Villeval J. L. et al. (1987) Characterization of the blast population in two neonates with Down's Syndrome and transient myeioproliferative disorder. Br. J. Haemat. 66, 69. 6. Kuruhashi H., Junichi H. & Keiko Y. et al. (1991) Monoclonal nature of transient abnormal hematopoiesis in Down's Syndrome. Blood 77, 1161. 7. Doyle J., Poon A. & Zipursky A. (1991) Transient leukemia and Down syndrome. Blood 78, 41a. 8. Becroft D. M. O. & Zwi J. (1990) Perinatal visceral fibrosis accompanying the megakaryoblastic leukemoid reaction of Down Syndrome. Pediat. Path. 10, 397. ALVIN ZIPURSKY JOHN DOYLE Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada 195

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Page 1: Leukemia in newborn infants with down syndrome

Leukemia Research Vol. 17, No. 2, p. 195, 1993. 0145-2126/93 $6.00 + .00 Printed in Great Britain. © 1993 Pergammon Press Ltd

LETTER TO THE EDITORS

LEUKEMIA IN NEWBORN INFANTS WITH DOWN SYNDROME

(Received 6 August 1992. Accepted 22 August 1992)

THE LETTER from Dr K. Ghosh, entitled "Transient abnormal myelopoiesis in Down syndrome--are some of them truly leukemia?", published in Leu- kemia Research, 16, 545 (1992) was of great interest to us. There are several features of the case which are unique and different from previously published cases of transient abnormal myelopoiesis or transient leukemia in Down syndrome [1]. The first is the very high count of blasts in the peripheral blood (209 × 109/0, the second is the high percentage of blasts in the bone marrow (95%), and the third is the presence of monosomy 7 in blood cells.

The presence of monosomy 7, a clonal population, was interpreted by Dr Ghosh as evidence that tran- sient leukemia in Down syndrome is leukemia. Although cytogenetic abnormalities are not common in transient leukemia they do occur and in addition to the case described in Dr Ghosh's letter and one report cited therein we have seen one case of tran- sient leukemia with tetrasomy 21 and one in which the karyotype of the leukemic cells was 47xy + 21 der(5) t(1; 5) (q25; q32). There have been other reports of chromosomal abnormalities in the leu- kemic cells of transient leukemia including pen- tasomy 21 [2] and an x-8 translocation [3]. Also one case has been reported [4] in which an additional C chromosome was found in the leukemic cells at birth; the patient developed acute megakaryoblastic leu- kemia several years later at which time the initial chromosomal abnormality re-appeared.

We support Dr Ghosh's speculation that transient leukemia may be leukemia. In addition to the cyto- genetic data cited above we believe there is sub- stantial evidence to support this thesis:

1. The cells in the blood have been identified as megakaryoblasts [5].

2. The proliferation of megakaryoblasts in transient leukemia is clonal [6].

3. In approximately 20% of cases, acute mega- karyoblastic leukemia will develop [1].

4. In some cases, the disease is fatal or life threat- ening due to hydrops and/or congestive heart fail- ure [7].

5. In fatal cases, postmortem studies reveal leukemic infiltration with or without fibrosis in liver and other tissues [8].

We conclude therefore that transient leukemia in Down syndrome is leukemia that usually disappears spontaneously but may be persistent or fatal, and may recur as acute megakaryoblastic leukemia.

REFERENCES

1. Zipursky A., Poon A. & Doyle J (1992) Leukemia in Down Syndrome: a review. Pediat. Hemat. Oncol. 9, 139.

2. Rogers P. C. J., Thomas J. W. & Kalousek D. K. et al. (1983) Neonate with Down's Syndrome and transient congenital leukemia. Am. J. Ped. Hem./Onc. 5, 59.

3. Lazarus K. H., Heerema N. A. & Palmer C. G. et al. (1981) The myeloproliferative reaction in a child with Down Syndrome: cytological and chromosomal evi- dence for a transient leukemia. Am. J. Hemat. 11,417.

4. Honda F., Punnett H. H. & Charney E. et al. (1964) Serial cytogenetic and hematologic studies on a mongol with trisomy 21 and acute congenital leukemia. J. Pediat. 65, 880.

5. Coulombel L., Derycke M. & Villeval J. L. et al. (1987) Characterization of the blast population in two neonates with Down's Syndrome and transient myeioproliferative disorder. Br. J. Haemat. 66, 69.

6. Kuruhashi H., Junichi H. & Keiko Y. et al. (1991) Monoclonal nature of transient abnormal hematopoiesis in Down's Syndrome. Blood 77, 1161.

7. Doyle J., Poon A. & Zipursky A. (1991) Transient leukemia and Down syndrome. Blood 78, 41a.

8. Becroft D. M. O. & Zwi J. (1990) Perinatal visceral fibrosis accompanying the megakaryoblastic leukemoid reaction of Down Syndrome. Pediat. Path. 10, 397.

ALVIN ZIPURSKY JOHN DOYLE

Division of Hematology/Oncology, The Hospital for Sick Children,

Toronto, Ontario, Canada

195