|
A 52-year-old man was admitted to
the hospital because of fever, shaking chills, productive
cough, epistaxis, and hemoptysis for 2 days. The patient was
well until one month prior to admission, when he developed
pale appearance and petechiae over bilateral lower
extremities. He was diagnosed as acute promyelocytic leukemia
with disseminated intravascular coagulation after a series of
examinations, including bone marrow aspiration, peripheral
blood smear and coagulation study. Genetic study showed a t
(15,17) translocation. Then, all-trans retinoic acid (ATRA)
was administered. An episode of left lower lobe pneumonia was
also noted. He was put on ceftazidime and tobramycin. Fever
and productive cough gradually subsided in one week.
Concurrent chemotherapy with
idarubicin and cytarabine (I2A2) was given on the 9th and 10th
days after all-trans retinoic acid
treatment. Intermittent fever without shaking chills or
rigors developed nine days after all-trans retinoic acid treatment.
Besides, he experienced progressive edema with arthralgia
over bilateral ankles, gross hematuria, bloody stool
and aggravated hemoptysis. Acute oliguric renal failure and progressive
respiratory distress were also noted two weeks after
all-trans retinoic acid treatment. He then underwent further
evaluation.
He was a building security without
history of exposure to radiation or chemicals. He had
hyperuricemia for years without regular medical control. He
denied habits of smoking and alcohol consumption. His mother
had hypertension and diabetes mellitus and died of heart
disease.
The body temperature was 40 ℃ at
examination. The pulse rate was 120/min. The respiration rate
was 28/min. The blood pressure was 110/70 mmHg. Inspiratory
crackles over bilateral upper and lower lung fields with mild
decreased lung sound over bilateral lower lung fields were
found. The heart examination was unremarkable. The bowel sound
was normoactive. The abdomen was soft without tenderness.
There was no hepatosplenomegaly. There was no lymphadenopathy.
Bilateral pedal swelling and petechiae were noted. A rectal
examination showed external hemorrhoids and no palpable
mass.
< Laboratory Data >
1. CBC + D/C:
| Days after ATRA treatment |
RBC(M/μl) |
Hb(g/dl) |
Hct(%) |
MCV(fl) |
MCHC(%) |
PLT(K/μl) |
WBC( /μl) |
| D01 |
2.14 |
6.8 |
20.2 |
94.4 |
33.7 |
75 |
4630 |
| D09 |
2.81 |
8.6 |
25.3 |
90.0 |
34.0 |
110 |
3420 |
| D13 |
2.62 |
8.2 |
23.7 |
90.5 |
29.3 |
63 |
2000 |
| D23 |
2.61 |
7.6 |
22.1 |
84.7 |
34.4 |
45 |
1910 |
| D28 |
3.26 |
9.5 |
27.2 |
83.4 |
34.9 |
61 |
550 |
| D34 |
2.83 |
8.2 |
23.9 |
84.5 |
34.3 |
120 |
4240 |
| Days after ATRA treatment |
Myelo-blast(%) |
Promye-locyte(%) |
Myelo-cyte(%) |
Meta(%) |
Band(%) |
Seg(%) |
Eos(%) |
Baso(%) |
Mono(%) |
Lym(%) |
| D01 |
1 |
92 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
7 |
| D09 |
0 |
28 |
21 |
4 |
5 |
6 |
0 |
0 |
0 |
36 |
| D13 |
0 |
0 |
5 |
7 |
10 |
47 |
3.5 |
5.5 |
2 |
20 |
| D23 |
0 |
0 |
1 |
0 |
6 |
85 |
0 |
0 |
1 |
7 |
| D28 |
0 |
0 |
0 |
0 |
4 |
62 |
0 |
0 |
8 |
26 |
| D34 |
0 |
0 |
0 |
0 |
0 |
71.8 |
0.2 |
0.2 |
17.9 |
9.9 |
2. BCS
| Days after ATRA treatment |
A/G(gm/dl) |
Bil(T/D)(mg/dl) |
AST(U/l) |
ALT(U/l) |
ALP(U/l) |
r-GT(U/l) |
LDH(U/l) |
BUN(mg/dl) |
Cre(mg/dl) |
UA(mg/dl) |
| D01 |
3.1/3.3 |
0.8/0.3 |
24 |
14 |
129 |
75 |
1501 |
18.9 |
0.9 |
6.1 |
| D08 |
3.3/3.9 |
0.7/0.2 |
44 |
39 |
181 |
70 |
1049 |
18.8 |
0.9 |
4.6 |
| D17 |
2.9/3.7 |
0.9/0.2 |
21 |
12 |
170 |
54 |
754 |
48.1 |
2.8 |
8.0 |
| D21 |
2.7/3.4 |
1.1/0.7 |
19 |
6 |
139 |
59 |
894 |
98 |
7.3 |
7.7 |
| D23 |
2.9/3.8 |
1.1/0.7 |
21 |
8 |
138 |
61 |
897 |
117.5 |
8.9 |
7.6 |
| D26 |
3.0/4.0 |
0.8/0.5 |
13 |
4 |
147 |
75 |
|
196.1 |
11.2 |
10.4 |
| D52 |
3.2/3.9 |
0.6/0.2 |
8 |
9 |
|
|
|
53.9 |
2.2 |
5.2 |
3. PT/PTT and DIC
profile
| Days after ATRA treatment |
PT(sec) |
PTT(sec) |
3P test |
D-dimer(μg/ml) |
FDP (μg/ml) |
Fibrinogen(mg/dl) |
| D01 |
17.4/11.9 |
37.3/32.0 |
4+ |
16-32 |
160-320 |
188 |
| D08 |
12.1/11.8 |
31.3/33.2 |
- |
0.5-1 |
10-20 |
318 |
| D16 |
|
|
4+ |
6.02 |
20-40 |
296 |
| D22 |
16.8/11.5 |
42.0/32.3 |
2+ |
1.65 |
10-20 |
393 |
| D26 |
16.6/11.5 |
35.1/31.3 |
- |
1.50 |
10-20 |
400 |
4.
Urinalysis
| Days after ATRA treatment |
PH |
Protein(mg%) |
Sugar(mg/dl) |
OB |
Ketone |
Bili-rubin |
Urobili-nogen |
RBC(/HPF) |
WBC(/HPF) |
Cast |
| D02 |
6.5 |
>300 |
- |
3+ |
- |
- |
0.1 |
60~70 |
2-5 |
Hy(2~3) |
| D10 |
7.0 |
30 |
- |
3+ |
- |
- |
0.1 |
12-15 |
3-5 |
- |
| D15 |
6.0 |
30 |
- |
3+ |
- |
- |
0.1 |
Num |
2-4 |
RBC dys-morphism (-)Cylindoid (+) |
| D24 |
6.0 |
30 |
- |
3+ |
- |
- |
0.1 |
Num |
1-3 |
- |
5. Blood gas
| Days after ATRA treatment |
PH |
PCO2(mmHg) |
PO2(mmHg) |
HCO3(mEq/l) |
BE(mEq/l) |
|
| D23 |
7.37 |
26.9 |
186.1 |
15.1 |
-9.0 |
FiO2 60%, 10 L/min |
| D26 |
7.33 |
23.2 |
316.5 |
11.9 |
-12.8 |
FiO2 36%, 5 L/mim |
6. Blood culture:
(2000/01/24, D01) No aerobic & anaerobic pathogens
(2000/02/08, D16) No aerobic & anaerobic pathogens
(2000/02/14, D22) No aerobic & anaerobic pathogens
7. Sputum culture:
(2000/01/22, D-02) Klebsiella pneumoniae
(2000/02/10, D18) Sternotrophomonas maltophilia
8. Bone marrow examination
(2000/01/24, D01) Acute promyelocytic leukemia, t (15;17)
(2000/02/14, D22) Acute promyelocytic leukemia, in good
partial remission (2000/02/29, D37) Hypocellular marrow,
moderate, in complete remission
9. Renal echo: parenchymal renal disease
 Course and treatment
After
fever work-up, the antibiotics were shifted to cefepime,
amikacin, and clarithromycin under the impression of bilateral
pedal cellulitis. However, the fever persisted. Vancomycin,
imipenem, and fluconazole were used to replace cefepime,
amikacin and clarithromycin. Cultures from blood and urine did
not yield microorganism. The respiratory distress became more
and more severe. Acute renal failure was noted two weeks after
Tretinoin (ATRA) therapy. Furosemide (240 mg/day iv infusion)
was given for oliguria and vancomycin was discontinued. Serum
aminoglycoside levels were within therapeutic ranges and uric
acid levels within normal limits. The urine output increased
about three days later and furosemide was tapered. However,
exacerbated azotemia, accompanied with uremic symptoms
occurred and hemodialysis was performed. Serial chest X-ray
showed progressive infiltration over bilateral lung fields(圖一). High resolution
computerized tomography(圖二 ) revealed
multifocal infiltration of bilateral lungs, consolidation
at left lower lung, increased infiltration with
focal ground glass opacities at right lower lung, and
bilateral pleural effusion. Cardiac echo showed fair LV contractility
without pericardial effusion. Due to intermittent high
fever refractory to strong antibiotics, progressive respiratory
distress, acute renal failure, increased pulmonary
infiltrate with pleural effusion, all-trans retinoic
acid syndrome was suspected. Tretinoin was discontinued and
dexamethasone ( 20mg/day) was administered. Fever subsided
12 hours after the treatment. Besides, the respiratory distress
also improved dramatically. The follow-up chest X-ray
showed gradual resolution of pulmonary infiltrate.He also
recovered from the episode of acute renal failure soon.
Bone marrow examination thirty-seven days after all-trans retinoic
acid treatment showed complete remission of acute promyelocytic
leukemia.
|
Case Discussion