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| Year : 1983 | Volume
: 29
| Issue : 1 | Page : 15-9 |
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Raised foetal haemoglobin in haematological malignancies. (A study of 97 cases).
MB Agarwal, BC Mehta, SS Rao
Correspondence Address:
M B Agarwal
How to cite this article:
Agarwal M B, Mehta B C, Rao S S. Raised foetal haemoglobin in haematological malignancies. (A study of 97 cases). J Postgrad Med 1983;29:15-9
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How to cite this URL:
Agarwal M B, Mehta B C, Rao S S. Raised foetal haemoglobin in haematological malignancies. (A study of 97 cases). J Postgrad Med [serial online] 1983 [cited 2023 Mar 25 ];29:15-9
Available from: https://www.jpgmonline.com/text.asp?1983/29/1/15/5564 |
Full Text
INTRODUCTION
Acquired rise in the level of foetal hemoglobin has been reported in various haematological malignancies.[2], [6], [8] Sheredan et al[8] had shown that the maximum acquired rise in the foetal Hb is seen in juvenile chronic myeloid leukemia and erythroleukemia. Following is an account of certain as yet unstudied characteristics regarding the acquired rise in foetal hemoglobin seen in different haematological malignancies at our department over the last four years from 1978 to 1981.
MATERIAL AND METHODS
Patients of haematological malignancy attending our department were studied for foetal Hb, HbA2, red cell inclusion bodies and the presence of abnormal hemoglobin. All the initial studies were carried out prior to blood transfusion. Foetal Hb was estimated by Singer's one minute alkali denaturation method.[9] HbA2 was estimated by elution after paper electrophoresis.[4] The intracellular distribution of Hb-F was examined by the acid elution method.[4] A search was made for the inclusion bodies in supravitally stained peripheral smear.
Overall 97 cases of different haematological malignancies were studied [Table 1] As the normal Hb-F in our laboratory controls ranged from 0.1 to 1.96% (mean: 0.9 ± 0.32), any rise in its level above this was considered abnormal. Foetal Hb was repeated in 26 cases of chronic myeloid leukaemia (CML) after the reduction in the total leukocyte count to under 15,000/cmm following chemotherapy. None of these had received any transfusion. Similar studies were done in 11 cases of acute lymphoblastic leukaemia and 6 cases of acute non-lymphoblastic leukaemia after achieving initial remission and at least 1 month after the last transfusion. An attempt was made to study the effect of age at onset of the disease on the incidence and the degree of rise in foetal haemoglobin.
RESULTS
The overall incidence and the degree of raised haemoglobin-F values in different haematological malignancies are shown in [Table 1]. None of the cases showed any abnormal Hb or increase in the amount of Hb-A2. Similarly, no inclusion bodies were seen in the red cells in any case. Hb-F showed heterogenous intraerythocytic distribution in all the cases. The effect of age at onset of the disease on the rise of Hb-F is shown in [Table 2]. The alteration in Hb-F level after treatment is shown in [Table 3].
DISCUSSION
After the first year of life, Hb-F usually does not account for more than of the total haemoglobin.[4] Levels higher than this are commonly seen in haemoglobinopathies (thalassemia, HPHF or abnormal haemoglobins). Investigation of foetal haemoglobin in other haematological disorders have shown it to be significantly raised in a number of benign or malignant acquired haematological disorders.[7], [8], [11]
In the present study, over one third of the cases of haematological malignancies were shown to have an acquired rise in foetal hemoglobin. The incidence and degree of rise in foetal Hb were variable in different disorders. Maximum rise was seen in juvenile chronic myeloid leukemia, where both cases had very high level of foetal Hb (28.2% and 32.6%) together with practically insignificant amount of HbA2 (i.e. 0.1 and 0.3%). Parents of both these cases showed no evidence of haemoglobinopathies. In the present series, cases of erythroleukemia did not show markedly raised HbF level (HbF: 5.4 and 8.2%). This was rather unusual as majority of the cases of erythroleukemia reported in the literature have shown HbF above 10%.[8]
An interesting feature was the occurrence of raised foetal Hb in more than half of the cases of haematological malignancies in children under the age of 10 years, while this was seen in only 35.4% of the cases over 10 years. The difference was statistically significant (p <0.05). In half of the cases where HbF was repeated after induction of remission in acute leukemia or after controlling the total leukocyte count in CML, the amount of HbF had increased. In one third of cases, the HbF levels had decreased while in the remaining it had remained constant. There was no obvious clinical or laboratory feature to predict alteration in HbF level and its clinical significance remains obscure.
Production of foetal proteins by malignant tissue is a recognised feature seen in many neoplastic disorders.[1] It is difficult to arrive at any significant conclusion regarding the need and the mechanism for the switch over from adult to foetal hemoglobin production in these different disorders. That this is not secondary to hypoxic stress on the marrow is clear as foetal Hb has not been shown to rise in congenital cyanotic heart diseases.[3] In JCML and EL, Weatheral has shown a genuine reversion to foetal erythropoiesis.[10] The fact that this reversion occurs more commonly in children may suggest that it may be affecting the basic mechanism by which the gamma chain synthesis is replaced by beta chain synthesis after birth.
It has been stated that some of the cases may show raised foetal Hb as an effect of rapid regenerative process occurring after the aplasia due to the treatment used in leukemia.[8] However, this does not appear to explain the whole problem as not all cases show rising Hb-F during the recovery phase. Interestingly, in a similar study, it was concluded that only myelogenous leukemias are characterised by acquired rise in foetal haemoglobin.[5] However, from the present study this definitely appears to be disproven.
Overall, the present study shows that foetal Hb rises in a significant number of cases of haematological malignancies. There appears to be no consistent relationship between the rise of foetal Hb and the nature or stage of malignancy and its response to treatment. Children with haematological disorders do show raised foetal Hb more often.
ACKNOWLEDGEMENT
We are thankful to Dr. C. K. Deshpande, Dean, Seth G. S. Medical College and K.E.M. Hospital for permission to publish this paper. Part of the work was supported by grants from Seth G. S. Medical College and K.E.M. Hospital Research Society.
References
| 1 | Alexander, P.: Foetal antigens in cancer. Nature, 235: 137-138,1972. |
| 2 | Bartolozzi, G. and Marianelli, L.: Estimation of foetal haemoglobin in leukemia. Acta Haematol., 35: 214-220, 1966. |
| 3 | Coghlan, M. K. and Joseph, M. C.: The disappearance of HbF in congenital heart diseases. Arch. Dis. Childhealth, 33: 191-192, 1958. |
| 4 | Dacie, J. V. and Lewis, S. M.: "Practical Haematology", 5th Edition, Churchill, Livingstone, Edinburgh, London and New York, 1975, p. 236. |
| 5 | Dasgupta, A., Pavri, R. S. and Advani, S. H.: Hemoglobin abnormalities in haematological malignancies. Ind. I. Med. Res., 73: 82-89, 1981. |
| 6 | Miller, D. R.: Raised foetal haemoglobin in childhood leukemia. Brit. J. Hematol., 17: 103-112, 1969. |
| 7 | Shahidi, N. T., Gerard, P. S. and Diamond, L. K.: Alkali resistant hemoglobin in aplastic anemia of both acquired and congenital types. New Engl. J. Med., 266: 117-120, 1962. |
| 8 | Sheridan, B. L., Weatherall, D. J., Clegg, J. B., Pritchard, J., Wood, W. G., Callender, S. T., Durrant, I. J. McWhirter, W. R., Ali, M., Partridge, W. and Thompson, E. N.: The patterns of foetal haemoglobin production in leukemia. Brit. J. Hematol., 32: 487-506, 1976. |
| 9 | Singer, K., Chernoff, A. I. and Singer, L.: Studies of abnormal Hbs I. Their demonstration in sickle cell anemia and other hematological disorders by means of alkali denaturation. Blood, 6: 413-418, 1951. |
| 10 | Weatherall, D,. J., Edwards, J. A. and Donohoe, W. T. A.: Haemoglobin and red cell enzyme changes in juvenile myeloid leukemia. Brit. Med. J., 1: 679-681, 1963. |
| 11 | Weatherall, D. J., Pemberg, M. E. and Pritchard, J.: Foetal haemoglobin. Clinics in Haematology, 3: 467-508, 1974. |
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