Cobalamin deficiency during treatment of pediatric precursor B-cell
lymphoblastic leukemia
Hiromi Kinoshita1), Atsuko
Watanabe2), Yoshitada Taji1), Moe
Yoshimura2), Atsuhiko Ota2), Takashi
Fukushima2), Ryuhei Tanaka2),
Yasuhiro Ebihara1, 3)
1) Clinical Laboratory, 2)Department of Pediatric Hematology/Oncology, 3)Department of Laboratory Medicine, Saitama Medical University
International Medical Center, Saitama, Japan
Corresponding author: Yasuhiro Ebihara, MD, Department of Laboratory
Medicine, Saitama Medical University International Medical Center,
1397-1 Yamane, Hidaka-shi, Saitama 350-1298, Japan
TEL: +81-42-984-4384; FAX: +81-42-984-4384E-mail:ebihara@saitama-med.ac.jp
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Figure: 1
Supplementary Table: 1
Running title: Cobalamin deficiency in pediatric BCP-ALL
Keywords: cobalamin deficiency, pediatric B-cell precursor acute
lymphoblastic leukemia, erythroid dysplasia, nutrition
To the editor,
There has been considerable progress in supportive therapy and care
strategies for patients with cancer, but nutritional problems may still
arise during treatment 1. Herein, we report on a
4-year-old boy who was diagnosed with B-cell precursor acute
lymphoblastic leukemia (BCP-ALL). Complete remission was achieved and
maintained. Eight months later, he underwent late intensification
treatment, which contained three cycles of methotrexate 500
mg/m2. BM examination scheduled before he went into
the maintenance phase showed erythroid dominance and apparent dysplasia,
including megaloblastic change, multinuclearity, karyorrhexis, and
nuclear budding, and a few Howell-Jolly bodies were noted in the
cytoplasm of some erythroid cells (Figure 1). Myelodysplastic syndrome
(MDS) was suspected because he had received several anti-leukemic drugs
that could induce treatment-related MDS. These morphological changes are
seen in folate and/or cobalamin deficiency, which might be mistaken for
MDS or acute leukemia 2, 3. The
laboratory investigations (Table S1) revealed a decreased serum
cobalamin level of 145 pg/mL, indicating that the erythroid dysplasia
was due to cobalamin deficiency. Oral replacement therapy of
mecobalamin, 500 µg/day, was started. Ten days later, BM examination
revealed that the erythroid dysplasia had mostly disappeared. The final
diagnosis was erythroid dysplasia caused by cobalamin deficiency. The
patient subsequently underwent maintenance treatment and has remained in
CR.
A characteristic feature of cobalamin deficiency is nuclear-cytoplasm
asynchrony in erythroid maturation, whereby maturation of the nucleus is
delayed relative to that of the cytoplasm because cobalamin is essential
for DNA synthesis 4, 5. Cobalamin
deficiency is very rare in childhood, and is seen mainly in children
with inadequate intake, breast-feeding infants with a
cobalamin-deficient mother, and those with congenital malabsorption4, 5. The occurrence of cobalamin
deficiency in the middle of the ALL treatment is extremely rare for the
pediatric patients who can take orally and developing normally. In
pediatric ALL patients, the existence of cobalamin deficiency before
treatment was reported 6,7, but there is almost no
report about cobalamin deficiency during treatment. We could not find
any factors which might induce cobalamin deficiency. However, it was
possible that the repeated episodes of BM suppression, the recovery from
which required more cobalamin for maturation of blood cells, and
accumulation of anorexic episodes a caused by administration of
anti-leukemic drugs and treatment complications might have led to a
gradual decrease in his serum cobalamin level, culminating in cobalamin
deficiency. Cobalamin deficiency requires parenteral or oral replacement
therapy 4, 8. It is reported that
response to replacement is rapid (within 5 days) and megaloblastic
anemia can be corrected in 6-8 weeks 4,5. However, the erythroid dysplasia in BM resolved
almost completely after 10 days of cobalamin replacement, and
improvement in both peripheral blood (Table S1) and BM were clearly
achieved in our patient. Although there have been reports of improved
laboratory data in peripheral blood 2,4, 5, there are few descriptions on
findings in BM 9. Although there has been considerable
progress in supportive therapy and care strategies for children with
cancer, their nutritional status should be monitored carefully during
treatment.