Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1094-1095
CORRESPONDENCE
Disappearance of Cytogenetic Abnormalities Induced by
Cyclosporine Therapy in a Case of Aplastic Anemia
 |
LETTER |
To the Editor:
We report a patient with aplastic anemia (AA) who exhibited cytogenetic
abnormalities at presentation, but who recovered hematologically with
disappearance of cytogenetic abnormalities after cyclosporine (CyA)
therapy.
A 55-year-old woman presented to our hospital in September 1995 with
breathlessness on exertion of 1-month duration. She was pale, and
petechiae were observed on her skin. A hemogram revealed severe
pancytopenia with hemoglobin (Hb) 3.8 g/dL, granulocyte count 0.35 × 109/L, platelet count 13 × 109/L, and
reticulocyte count 11 × 109/L. Serum lactate
dehydrogenase, bilirubin, and haptoglobin were within normal range.
Bone marrow examination showed a severely hypocellular marrow with
depression of all three hematopoietic cell lines, and no dysplastic
features. The same findings were obtained on trephine biopsy. Magnetic
resonance imaging of the lumbar spine revealed homogeneously fatty
marrow. Therefore, the diagnosis of AA was made. Oral CyA therapy at a
daily dose of 350 mg in combination with 300 µg/m2 of
filgrastim for 4 weeks and pulse therapy with methylprednisolone was
started in September 1995. There was a gradual response of all three
cell lines, and she became completely independent of blood transfusions
about 1 year later. CyA was then carefully tapered to 100 mg twice
daily. As of September 1997, she is maintaining Hb > 8 g/dL,
granulocyte count > 1.0 × 109/L, and platelet count > 50 × 109/L. Bone marrow examination performed in March
1997 showed a nearly normocellular marrow and no dysplastic features
other than a few binucleated erythroblasts. Cytogenetic analyses of
bone marrow cells were serially performed. As summarized in Table
1, on analyses performed in September 1995 (initial presentation), October 1995, and January 1996 (4 months after
initiation of treatment), cytogenetic abnormalities chiefly involving
the short arm of chromosome 1 (1p) were detected in 30% to 37.5% of
metaphases analyzed. However, since 5 months after initiation of
treatment, no cytogenetic abnormalities were detected in four analyses
performed.
Immunosuppressive therapies such as antithymocyte globulin and CyA have
been used successfully to treat AA,1,2 and immune-mediated suppression of hematopoiesis has therefore been considered the most
important mechanism responsible for bone marrow failure in AA.3 However, recent studies have shown that long-time
survivors of AA after immunosuppressive therapy are at high risk of
developing myelodysplastic syndrome (MDS) and acute myelogenous
leukemia, in which clonal cytogenetic abnormalities commonly are
present.4 This suggests that clonal abnormalities of stem
cells also play a role in the pathophysiology of AA. Although
cytogenetic abnormalities have infrequently been reported in patients
with AA at presentation, Applebaum et al5 reported that
seven of 176 patients with AA had clonal cytogenetic abnormalities at
presentation, and that 2 of these 7 cases evolved into MDS.
Interestingly, in the present case, chromosomal abnormalities detected
at presentation disappeared after initiation of immunosuppressive
therapy with CyA. Although it is unclear whether these cytogenetic
abnormalities were chiefly responsible for bone marrow failure in the
present case, our findings suggest that both immunological mechanisms
and clonal hematopoietic abnormalities may play roles in the
pathogenesis of AA.
Minoru Takeshima
Yasuhiro Mochizuki
Takashi Yoshida
Department of Internal
Medicine
Toyama Prefectural Central Hospital
Toyama,
Japan
Hideyuki Takamatsu
Department of Internal
Medicine
Kurobe City Hospital
Kurobe, Japan
Hirokazu Okumura
The 3rd Department of Internal Medicine
School of
Medicine
Kanazawa University
Kanazawa, Japan
| |
REFERENCES |
1.
Young NS,
Griffin P,
Brittain E,
Elfenbein G,
Gardner F,
Huang A,
Harmon D,
Hewlett J,
Fay J,
Mangan K,
Morrison F,
Sensenbrenner L,
Shadduck R,
Wang W,
Zalouris C,
Zuckermann K:
A multicenter trial of antithymocyte globulin in aplastic anemia and related disease.
Blood
72:1989,
1989
2.
Gluckman E,
Esperou-Bourdeau H,
Baruchel A,
Boogaerts M,
Briere J,
Donadio D,
Leverger G,
Leporrier M,
Reiffers J,
Janvier M,
Michallet M,
Stryckmans P:
Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia.
Blood
79:2540,
1992[Abstract/Free Full Text]
3.
Frickhofen N,
Liu JM,
Young NS:
Etiologic mechanisms of bone marrow failure.
Am J Pediatr Hematol Oncol
12:385,
1990[Medline]
[Order article via Infotrieve]
4.
Socié G,
Henry-Amar M,
Bancigalupo A,
Hows J,
Tichelli A,
Ljungman P,
McCann SR,
Frickhofen N,
Veer-Korthof EV,
Gluckman E:
Malignant tumors occurring after treatment of aplastic anemia.
N Engl J Med
329:1152,
1993[Abstract/Free Full Text]
5.
Applebaum FR,
Barrall J,
Stork R,
Ramberg R,
Doney K,
Sale GE,
Thomas ED:
Clonal cytogenetic abnormalities in patients with otherwise typical aplastic anemia.
Exp Haematol
15:1134,
1990
