[Reprinted irom the Boston Medical and Surgical Journal 
of August 9, 1894.] 
LEUKEMIA IN INFANTS. 
BY #OHN LOVETT MORSE, A.M., M.D., 
rhysician to Out-Patients at the Boston City Hospital and at the 
West End Nursery and Infants' Hospital. 
Little is known concerning the etiology of this 
disease. Several cases are on record which prove that 
a pregnant woman with leukemia cannot directly trans- 
mit it to her offspring. Cameron 1 reports a case where 
the child of a leukemic mother died on the fourth day, 
and the autopsy failed to reveal any evidences of leu- 
kemia. Greene,2 also, reports a case in which a leu- 
kemic mother was delivered of a healthy child. San- 
ger 8 had a case where a leukemic mother gave birth 
to a healthy child which did not develop leukemia, 
although kept under observation for some time, while 
in Degle’s 4 case the child was feeble but showed no 
signs of leukemia. Askanazy6 also reports a case 
where a woman with myelogenous leukemia was de- 
livered at full term of a slightly macerated fetus, 
which, on autopsy, showed no evidence of leukemia. 
On the other hand, Sanger8 reports a case in 
which a healthy woman was delivered of a dead- 
born fetus at the thirty-second week, which, on 
autopsy, showed well-marked signs of leukemia. It 
is possible, however, that the tendency to the disease 
may be transmitted. Several cases are on record of 
its occurrence in more than one member of the same 
family. Griffith 6 quotes cases of Casati7 and Eich- 
horst8 bearing on this point; while Osier9 relates a 
very interesting case of Cameron’s in which the dis- 2 
ease was present in three generations. Biermer 10 re- 
ports its occurrence in sisters, but it is hardly possible 
to rule out rhachitis in this instance. Senator’s11 
cases in twins are also open to the suspicion of anemia 
infantum pseudoleukemica. Ortner,12 also, saw the 
disease in sisters. 
Rhachitis is supposed to have some etiological con- 
nection with the disease in children, but its influence 
is probably not as great as has been supposed. It 
must be remembered in this connection that very few 
of the so-called cases of leukemia in children have 
been carefully worked up and reported. In very few 
has a blood count been made, and in only one or two 
has there been a differential count of the white corpus- 
cles. Fox and Ball18 in several hundred cases of 
rhachitis found the spleen enlarged in twenty-five per 
cent. In sixty-three cases of splenic tumor in infants, 
which they examined, rhachitis could not be positively 
excluded in one, and in almost all was very marked. 
In the few cases in which an examination of the blood 
was made nothing more than a slight leucocytosis was 
ever found. Carr 14 obtained the same results in a 
few cases which he examined. Kultner,18 also, speaks 
of the frequency of splenic tumor in rhachitis and calls 
attention to the ease with which splenic enlargement 
takes place in children. He examined the blood in 
ten cases, and in none of them found any evidence of 
leukemia. This frequent association of splenic tumor 
with rhachitis is undoubtedly the source of the com- 
mon acceptation of rhachitis as a cause of leukemia. 
It must be said, however, that rhachitis has been pres- 
ent in nearly all of the more carefully reported cases 
of leukemia in children. Its true relation, however, 
can only be determined by the examination of the 
blood by modern methods in a large number of cases. 
The same doubt hangs about the relation of syphilis 3 
to leukemia in children. Fox and Ball18 found the 
spleen enlarged in forty-eight per cent, of their cases 
of inherited syphilis, and in sixty-three cases of splenic 
tumor in iufauts, forty-one had inherited syphilis. The 
examination of the blood in these cases also showed at 
most a slight leucocytosis. 
Leukemia has sometimes developed in adults after 
trauma. Mosler 10 has reported a rather doubtful case 
of this sort in a child. 
The disease is most common in middle-life. Birch- 
Hirschfeld,17 in 1878, out of 201 cases collected by 
him, found only four under one year. Havem,18 in 
1879, expressed the opinion that only four or five 
cases had been seen in children under one year. Bag- 
insky,19 on the other hand, thinks that from fifteen to 
twenty per cent, of the cases are seen in children un- 
der ten years, and Gerhardt20 thinks it is as frequent 
in children as it is later in life. But little reliance 
can be placed on these figures, however, because of the 
possibilities of errors in diagnosis. 
Males are generally more prone to the disease than 
females. This rule seems to hold good, also, as re- 
gards children, so far as the figures are of use in so 
small a number of cases. 
I have been able to collect 20 cases of leukemia 
in infants out of literature. The diagnosis in the ma- 
jority, however, must be regarded as doubtful. In the 
earlier cases no examination of the blood was made, 
and in some of these the diagnosis rests entirely on the 
clinical picture, no autopsy having been made. In 
many of the later cases a blood count was made, but 
in very few has the character of the white corpuscles 
been noted, and in only one has a differential count of 
them been made. The doubt that surrounds them is 
well shown by the fact that each author in turn has 
been sceptical as to the accuracy of the diagnosis in 4 
most of the cases of his predecessors. It is highly 
probable that many of them were cases of rhachitis 
with splenic tumor and anemia, or of anemia with leu- 
cocytosis — the anemia infantum pseudoleukemica of 
v. Jaksch.21 In the future no such confusion will be 
possible, as a differential count of the white corpuscles 
makes the diagnosis positive. 
The cases, with dates and ages, are as follows : Gol- 
itzinsky,22 1861, two cases, eleven months and two 
weeks respectively; Hosier,16 1864, six months; 
Seitz,23 1866, one year; Stilling,24 1880, one year; 
Fagge,26 1881, twenty months ; Senator,11 1882, twins 
of eighteen months; Ballowitz,26 1884, five mouths; 
Litten,37 1887, eighteen months; Hochsinger and 
Schiff,28 1887, sixteen months; Sanger.8 1888, fetus 
at thirty-second week ; v. Jaksch,21 1889, fourteen 
months; Hayern,18 1889, ten months; Mayer,20 1890, 
sixteen months; Chaumier,80 1890, sixteen mouths; 
Ortner,12 1891, eight and a half months ; Middleton,31 
1893, sixteen months; Osier,9 1893, eight months; 
Engel,82 1894, thirteen months. It is highly proba- 
ble, however, that not more than half, perhaps not 
more than a third, of these were really cases of leu- 
kemia. 
My own case follows : Joe K., one year old, came 
to the West End Nursery ou April 26, 1894, as 
an out-patient. His parents were both Russians, and, 
although very poor, seemed well and strong. As far 
as they knew, no relatives had had any disease of this 
nature. No history of syphilis could be obtained. 
Four other children were alive, well and not rhachitic. 
Two had died of acute disease in Russia. No very 
definite history of his illness could be obtained. He was 
weaned at three mouths, and had been fed exclusively 
on condensed milk for the last six months. He had 
been failing gradually for some months, his belly had 5 
been large for two months, and he had been unable to 
lie on his left side for a month. Never had nose-bleed 
or hemorrhages from stomach or bowels. Never had 
any eruption on body. Vomited occasionally, bowels 
were somewhat constipated, the dejections being light- 
colored. No cough or pain. 
Physical examination showed a markedly atrophic 
child, very anemic. The head was large, forehead 
prominent, and anterior fontanelle widely open. Mod- 
erate rosary and enlargement of epiphyses, with slight 
bow-legs. Marked enlargement of glands in neck, 
axillae and groins. Heart and lungs normal. Abdo- 
men was very much enlarged but contained no fluid ; 
superficial veins distended. Liver dulness began at 
upper border of fifth rib in nipple line, and the lower 
border could be felt round and smooth about two fin- 
gers’ breadth below the costal border in the same line. 
The spleen was very much enlarged, coming from be- 
neath the costal margin just outside the parasternal 
line, running just outside the umbilicus, then beyond 
the middle line, filling up almost the whole left iliac 
region. The notch could be plainly felt. Spleen and 
abdomen not at all tender. No hemorrhagic spots on 
skin. The blood examination made at this time is 
given below. 
It was impossible to keep the child under observa- 
tion, but he was seen again on May 28. He had 
failed rapidly during the month. His skin was very 
pale with a decided yellow tinge, the face, body and 
extremities being thickly covered with purpuric spots, 
varying in size from that of a pin-head to that of a lead- 
pencil. These spots had appeared two days before, 
at which time he developed a cough, and refused to 
eat. Had had no other hemorrhages, bowels were 
loose, dejections of normal color, no vomiting. Ex- 
amination of the chest showed a broncho-pneumonia, 6 
involving the lower two-thirds of the left lung, and a 
well-marked bronchitis in the right. The heart was 
normal. Abdomen rather more distended, not tender, 
no fluid. There was a slight increase in the size of 
both liver and spleen. He was almost moribund, and 
probably survived but a few days. 
The usual association of leukemia with rickets was 
present in this case, the leukemia probably having de- 
veloped subsequent to the rhachitis. The latter was 
undoubtedly due to improper food and surroundings, 
and it seems more reasonable, in the present state of 
our knowledge, to consider the leukemia as arising 
from the same cause rather than as secondary to the 
rhachitis. 
The blood-count, made on April 26th, showed 
2,900,000 red corpuscles and 48,000 white per cubic 
millimetre, giving a proportion of one to sixty. A 
differential count of 1,000 white corpuscles on slips, 
dried and stained with Ehrlich’6 triple stain, resulted as 
follows : 
Small lymphocytes 234 = 23.4 % 
Large lymphocytes and transition forms . . 81= 8.1% 
Myelocytes 214 = 21.4% 
Polynuclear neutrophiles 465 = 46.5 % 
Eosinophiles 6 = .6 % 
The classification is that recommended by Thayer.83 
Slips stained with eosin and methylene-blue showed 
numerous mononuclear and polynuclear cells with fine 
granulations which took the eosinophile stain feebly. 
Slips stained with dahlia showed the presence of a 
very few “ mastzellen.” Numerous partially destroyed 
cells, both mononuclear and polynuclear, were met 
with. 
The red corpuscles were also of much interest, many 
forms being met with. There was a very marked 
poikilocytosis, a moderate number of microcytes, and 7 
many macrocytes, many of these being three times the 
diameter of a normal red corpuscle. Many of all these 
forms lacked the normal concavity. Nucleated red 
corpuscles were present in great abundance. No mi- 
croblasts were seen, however. Many cells, the size of 
normal corpuscles, were met with in which the nucleus 
was small, feebly stained, and with little nuclear struct- 
ure, the protoplasm being not quite homogeneous — 
“wrinkled,” as it were — and staining a reddish-vio- 
let. These may, perhaps, be regarded as undeveloped 
normoblasts. Normoblasts were very abundant, always 
with one nucleus, which showed a well-developed nu- 
clear structure, and which occasionally presented in- 
dentations, as if division was beginning. The nucleus 
was rarely in the centre, often on the side, sometimes 
half way out of the cell, and occasionally free. The 
protoplasm was ordinarily narrow, but sometimes wide. 
A few cells were met with from which the nucleus had 
probably escaped. Megaloblasts were quite numerous 
and presented the same variations as the normoblasts. 
In addition to these, a number of large oval cells were 
seen, which contained two nuclei, the long diameter of 
the cell being about four times that of a normal red 
corpuscle. In several of these well-marked karyokin- 
etic figures were present. These variations in the 
erythrocytes of course merely show a severe grade of 
secondary anemia. The presence of myelocytes in 
conjunction with the general glandular enlargement 
and the increased relative proportion of lymphocytes 
plainly places the case among the mixed forms of leu- 
kemia. 8 
1 Cameron : International Journal of the Medical Sciences, Janu- 
ary, 1888, i, 1. 
2 Greene : New York Medical Journal, February, 1888, xlvii.No. 6. 
s Siiuger : Archiv. f. Gynakol, 1888, Bd. 33, Heft 2. 
4 Degle : Wiener Med. Presse, 1891, xxxii, 416. 
8 Askanazy : Arcliiv. f. Patliolog. Anat. u. Phys., 1894, Bd. 137, 
Heft 1. 
6 Griffith : Keating’s Cyclopedia, iii. 783. 
7 Casati: Rivista Olinica, 2a ser., ii, 1872. 
s Eiclihorst: Spec. Path. u. Tlierap., 1886, iv, 3. 
® Osier: Practice of Medicine, 1893, 696. 
10 Biermer : Virchow’s Arcliiv., 1862, xxv, 142. 
11 Senator : Berlin klin. Woch., 1882, No. 35. 
]2 Ortner: Archiv. f. Kinderheilk, 1891, xxxii,252. 
13 Fox and Ball : British Medical Journal, 1892, i, 854. 
14 Carr : Lancet, 1892, i, 362. 
is Kultner : Berlin, klin. Woch., 1892, 1109. 
is Mosler : Berlin, klin. Woch., 1864, No. 12. 
17 Birch-Hirschfeld : Gejhardt’s Handb. d. Kinderkr., 1878, iii, i, 
309. 
is Hayem : Du Sang, 1889, 864. 
10 Baginsky : Lehrb. f. Kinderkr., 1887, 292. 
20 Gerhardt: Lehrb. f. Kinderkr., 1881, 276. 
21 V. Jaksch: Wien. klin. Woch., 1889, Nos. 22 and 23. 
22 Golitzinsky : Jalirb. f. Kinderheilk., 1861, 90. 
23 Seitz ; Deutsche Klinik, 1866, Nos. 15, 16. 
24 Stilling : Virchow’s Archiv., 1880, 80, 475. 
25 Fagge : Gerhardt’s Lehrb. f. Kinderkr., 1881, 276. 
28 Ballowitz : Inaug. Digs., Greit'swald, 1884. 
27 Litton : Berlin, klin. Woch., 1887. No. 35. 
28 Hochsinger and SchiiT: Vierteijahrschr. f. Dermat. u. Syphilis, 
1887, 14, 779. 
20 Mayer : Centralblatt. f. klin. Med., 1890, 21. 
30 Cliaumier : Poitou MOL, Poitiers, 1890, iv, 193-205. 
31 Middleton : Glasgow Medical Journal, 1893, xxxix, 356. 
32 Engel: Virchow’s Arcliiv., 1894, Bd. 135, s. 369. 
33 Thayer : Boston Medical and Surgical Journal, 1893, i, 156. 
REFERENCES.