Kidney transplantation in a patient with end stage renal disease after complete remission of acute promyelocytic leukemia.

Abstract

In general, a 2-yr disease-free duration is recommended before kidney transplantation (KT) in end-stage renal disease (ESRD) patients who also have acute leukemia. However, the optimal disease-free interval has not been specified for all subtypes of acute leukemia. Among these subtypes, acute promyelocytic leukemia (APL) shows a favorable prognosis and low relapse rate compared to other types of leukemia. We here report KT after complete remission (CR) of APL in an ESRD patient. Irreversible kidney injury developed in a 23-yr-old man with APL. First, we induced CR and subsequently performed KT 7 months after the achievement of CR. The patient's clinical course after KT was favorable, without allograft rejection or relapse of APL up to 1 yr after KT. On the basis of our clinical experience, it is suggested that a long wait may not be necessary before KT in patients with ESRD and APL.

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© 2012 The Korean Academy of Medical Sciences.
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pISSN 1011-8934
eISSN 1598-6357
Kidney Transplantation in a Patient with End Stage Renal Disease
after Complete Remission of Acute Promyelocytic Leukemia
In general, a 2-yr disease-free duration is recommended before kidney transplantation (KT)
in end-stage renal disease (ESRD) patients who also have acute leukemia. However, the
optimal disease-free interval has not been specified for all subtypes of acute leukemia.
Among these subtypes, acute promyelocytic leukemia (APL) shows a favorable prognosis
and low relapse rate compared to other types of leukemia. We here report KT after
complete remission (CR) of APL in an ESRD patient. Irreversible kidney injury developed in
a 23-yr-old man with APL. First, we induced CR and subsequently performed KT 7 months
after the achievement of CR. The patient’s clinical course after KT was favorable, without
allograft rejection or relapse of APL up to1 yr after KT. On the basis of our clinical
experience, it is suggested that a long wait may not be necessary before KT in patients with
ESRD and APL.
Key Words: Kidney Transplantation; Leukemia, Promyelocytic, Acute; End Stage Renal
Disease
Hyun Ji Chun1,2,3, Su Jeong Kim1,2,3,
In O Sun1,2,3, Byung Ha Chung1,2,3,
Ji-Il Kim3,4, In Sung Moon3,4,
Woo-Sung Min5, and Chul Woo Yang1,2,3
1Transplant Research Center, 2Division of
Nephrology, Department of Internal Medicine,
3Organ Transplantation Center, 4Department of
General Surgery, and 5Catholic Hematopoietic Stem
Cell Transplantation Center, Seoul St. Mary’s
Hospital, The Catholic University of Korea, Seoul,
Korea
Received: 10 January 2012
Accepted: 19 April 2012
Address for Correspondence:
Chul Woo Yang, MD
Department of Internal Medicine, Seoul St. Mary’s Hospital,
The Catholic University of Korea, 222 Banpo-daero, Seocho-gu,
Seoul 137-040, Korea
Tel: +82.2-590-2527, Fax: +82.2-536-0323
E-mail: yangch@catholic.ac.kr
This study was supported by a grant (A092258) from the Korea
Healthcare Technology R&D Project, Ministry of Health, Welfare
& Family Affairs, Republic of Korea.
http://dx.doi.org/10.3346/jkms.2012.27.7.814 • J Korean Med Sci 2012; 27: 814-817
CASE REPORT
Cell Therapy & Organ Transplantation
INTRODUCTION
Active malignancy in end-stage renal disease (ESRD) patients is
an absolute contraindication to kidney transplantation (KT) for
several reasons (1). First, immune suppression contributes to
the progression of cancer, which can significantly increase pa-
tient mortality (2). Indeed, the incidence of malignancy in KT
recipients is 2-20-fold higher than that in the general popula-
tion, depending on malignancy type (3). Second, early recur-
rence with associated morbidity and mortality would waste the
transplanted kidney. Therefore, most guidelines recommend a
2-yr disease-free duration before KT (4).
Leukemia is a hematologic malignancy with a relatively low-
er incidence than solid tumors (5). Only a few reports have de-
scribed KT after successful treatment of leukemia (6, 7). There-
fore, no specific recommendations for the timing of KT in ESRD
patients with leukemia are available. Instead, guidelines recom-
mend a 2-yr waiting period after the complete remission (CR)
of leukemia, as based on the guidelines for other types of malig-
nancy (2, 8).
Acute leukemia comprises many subtypes, which show a
highly variable clinical course. Of note, acute promyelocytic
leukemia (APL), a form of acute myeloid leukemia (AML; M3),
shows prominently favorable clinical outcomes compared to
other types of AML. Therefore, the waiting period before KT af-
ter CR of APL may not need to be as long as that recommended
for other types of leukemia in ESRD patients. However, no re-
ports have described KT after APL treatment using arsenic tri-
oxide (ATO). In this report, we describe successful living donor
KT in a young man who experienced CR of APL, treated with
ATO. Importantly, there has been no evidence of APL relapse
up to 1 yr after transplantation.
CASE DESCRIPTION
In December 2009, a 23-yr-old man visited the Department of
Emergency Medicine due to uncontrolled epistaxis, fatigue, and
weight loss. He did not have a specific medical history of inter-
est and specified that no abnormal findings were observed by
blood chemistry analysis or urinalysis during a health check-up
several months earlier. Laboratory analysis at presentation in-
dicated coagulopathy with a prothrombin time (international

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Chun HJ, et al. • Kidney Transplantation in Patient with ESRD and APL
http://jkms.org 815
http://dx.doi.org/10.3346/jkms.2012.27.7.814
normalized ratio) of 2.09, anemia, and thrombocytopenia with
46 × 109 platelets/L. White blood cell count was 6.5 × 109 cells/L
and hemoglobin level was 12.7 g/dL. Blood urea nitrogen and
serum creatinine (sCr) concentration was 21.6 mg/dL and 0.77
mg/dL, respectively. Lactate dehydrogenase level was 983 U/L,
C-reactive protein 22.59 mg/dL, D-dimer 104 μg/mL, and fibrin-
ogen 31 mg/dL, which was suggestive of severe disseminated
intravascular coagulation (DIC). On the peripheral blood smear,
leukocytes consisting of blasts (63%) and Auer rods were detect-
ed. All of these findings led us to suspect AML. We performed
bone marrow (BM) biopsy, and APL was diagnosed based on
the BM examination (Fig. 1). Cytogenetic molecular study us-
ing real-time quantitative polymerase chain reaction (RQ-PCR)
showed a promyelocytic leukemia/retinoic acid receptor-α
(PML-RARa) fusion transcript of 1.7 in the BM.
We initiated treatment for APL with daily all-trans retinoic
acid (ATRA) (25 mg/[m2 • day]) administration and idarubicin
(10 mg/day) administration on days 1 and 3. Three days after
the initiation of treatment, sudden dyspnea developed and bi-
lateral pulmonary infiltration was detected on chest Radiogra-
phy. We performed intubation and initiated ventilator care. At
this time, the patient’s renal function abruptly deteriorated. BUN
and sCr level increased to 99.6 mg/dL and 5.71 mg/dL, respec-
tively, and urine volume decreased to 200 mL/day. We changed
the patient’s treatment regimen to ATO monotherapy (0.15 mg/
[kg • day]) and initiated continuous renal replacement therapy
(CRRT) for acute renal dysfunction.
At 17 days after the start of ATO treatment, the patient was
successfully weaned off the ventilator, and his vital signs became
stable. However, his renal function did not recover, and his an-
uric state persisted. We converted CRRT to hemodialysis, which
was performed 3 times per week. The patient’s general condi-
tion improved thereafter, and he was discharged on hospital
day 35. During outpatient department follow-up, CR of APL was
detected by BM biopsy findings, and RQ-PCR revealed a PML-
RARa transcript of 0 at 3 months after the initiation of treatment.
After the achievement of CR, an additional 5 cycles of ATO
chemotherapy (10 mg/day, each cycle lasting 10 days, per 30 or
45 days.) were administered. However, the patient still showed
an anuric state and required maintenance hemodialysis thera-
py over the following 5 months. We performed kidney sonogra-
phy to assess the reversibility of the observed renal dysfunction.
Advanced chronic changes were detected, including decreased
kidney size: right 8.4 × 4 × 3 cm, left 8.5 × 4 × 3 cm, lobulated
contours, and increased parenchymal echogenicity (Fig. 2). Cor-
tical parenchymal blood flow was markedly decreased on the
color Doppler scan.
Up to 7 months after the achievement of CR, APL recurrence
was not detected by BM study or cytogenetic molecular study.
We therefore decided to perform KT using a kidney from the
patient’s younger sister. The HLA mismatch number was 2; the
panel reactive antibody titer was 0%, and the cross-match test
was negative. We administered triple immune suppressant ther-
apy consisting of tacrolimus 4 mg (level, 3-7 ng/dL), mycophe-
nolic acid 1,080 mg, and prednisolone 5 mg per day. After trans-
plantation, the patient showed immediate allograft function.
At 14 days after transplantation, sCr level fell from 10.26 mg/dL
to 1.32 mg/dL. We performed protocol biopsy at 3 months after
transplantation, which showed non-specific findings (Fig. 3).
Up to 1 yr after KT, the patient’s renal function has remained
stable, and no evidence of APL recurrence has been detected
by BM biopsy or molecular study performed at 1 yr after KT
(Fig. 4).
DISCUSSION
In this report, we describe the successful management of a com-
bined case of APL and ESRD in a young male patient. We initial-
Fig. 1. Bone marrow aspiration finding (Wright’s stain, × 1,000). Abnormal promyelo-
cytes with prominent cytoplasmic granules were found. It is consistent with acute pro-
myelocytic leukemia.
Fig. 2. Kidney ultrasonography finding. Before transplantation, ultrasonography showed
decreased kidney size (right 8.4 × 4 × 3 cm, left 8.5 × 4 × 3 cm) and lobulated
contour and increased parenchymal echogenicity (arrow). Above finding suggest the
advanced chronic change of kidney.

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816 http://jkms.org
http://dx.doi.org/10.3346/jkms.2012.27.7.814
ly performed chemotherapy to induce CR, and subsequently
performed KT. This sequential approach enabled us to over-
come both APL and ESRD in this patient without recurrence
of APL or deterioration of allograft function. To the best of our
knowledge, this is the first report of successful management in
a patient with both APL and ESRD.
First, as in all patients, we had to evaluate whether continued
dialysis or KT would be the most appropriate treatment strategy
in this patient. We believed that KT would be better suited than
dialysis, as this treatment option would allow us to perform au-
tologous hematopoietic stem cell transplantation (HSCT) as a
second-line therapy if APL recurred (9). In general, high-dose
chemotherapy during HSCT is not available to patients with
severe renal dysfunction (10). In addition, maintenance of he-
modialysis during the neutropenic state of HSCT can increase
the risk of fatal infection. In contrast, successful cases of BMT
in kidney transplanted state without deterioration of renal func-
tion or severe infection have been reported (11, 12). Therefore,
we elected to perform KT rather than continue dialysis treat-
ment.
Next, we had to determine the most appropriate timing of KT.
In general, it is recommended that KT in a patient with acute
leukemia and ESRD be performed 2 yr after CR, based on exist-
ing guidelines for other types of malignancy. However, specific
recommendations for such cases are currently unavailable, be-
cause only a few cases of combined acute leukemia and ESRD
have been reported. Thus, before determining the timing of KT,
we considered 3 factors, namely, CR, relapse, and risk factors.
In APL, the CR and 3-yr disease-free survival rate is nearly 90%,
which is significantly higher than that of other types of AML, at
just 50% (13). Further, the relapse rate of APL within 2 yr after
CR is only 6%, which is significantly lower than that of other
types of AML (14). Thus, APL differs from other types of AML
in that it is associated with a high CR rate and low relapse rate.
The present patient also could be categorized into the low-risk
group based on traditional risk factors such as age, performance
status, and gene study (14), as well as the newly recommended
risk model for APL based on WBC and platelet counts; in patients
with similar WBC and platelet counts to those observed in our
patient, the relapse rate has been reported to be nearly 0% over
more than 5 yr (15). Therefore, we performed KT earlier than
recommended (7 months after CR), because the risk of APL re-
currence was thought to be extremely low in this patient.
Another important consideration in this case was the revers-
ibility of the observed kidney dysfunction, because this patient
was a young man without underlying renal disease. The cause
of ESRD in this patient was unclear, but acute kidney injury may
have resulted from massive cortical necrosis due to severe DIC
combined with acute ATRA syndrome, which then progressed
to ESRD. The patient’s anuric state was sustained until KT, for
almost 9 months, and ultrasonography showed advanced chron-
ic changes in the kidney. These findings indicated that irrevers-
ible kidney injury had developed in this patient, thus necessi-
tating KT.
We observed the present patient for nearly 2 yr, including the
careful monitoring of APL relapse. The incidence of leukemia is
highest in the first year after transplantation, where after it shows
a decreasing pattern, in contrast to other malignancies, which
show an increasing incidence with time after transplantation (5).
Moreover, the incidence of de novo APL in renal transplant re-
cipients is extremely low. Only 3 patients presenting with new-
onset APL following KT have been reported in the past 3 decades
(16, 17). The above findings suggest that the risk of APL relapse
Fig. 3. Protocol allograft biopsy finding (H&E stain, × 100). Protocol biopsy performed
at 3 months after transplantation showed non-specific findings without tubulitis or
interstitial infiltration.
Fig. 4. Clinical course of the patient. CR was achieved at 3 months after the initiation
of treatment. Bone marrow biopsy was done total 6 times, four was done first every
month after CR and the last biopsy was performed at 17 month after CR, there is no
evidence of relapse. Until 9 months from the start of hemodialysis, renal function did
not recover and KT was performed. After KT, renal function was normalized immedi-
ately, and patient’s clinical course was stable until last follow up (2 yr). He is taking
triple immune suppressant; tacrolimus, mycophenolic acid, prednisolone. CRRT, con-
tinuous renal replacement therapy; HD, hemodialysis; KT, kidney transplantation; CR,
complete remission; RQ-PCR, Real-time quantitative polymerase chain reaction; BM
biopsy, bone marrow biopsy; Tac, Tacrolimus; MMF, mycophenolic acid.
Follow-up duration (months)
Serum creatinine
(mg/dL)
PML/RARA RQ-PCR
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
14
12
10
8
6
4
2
0
2.5
2
1.5
1
0.5
0

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in this patient is likely to be very low, as no signs of relapse were
observed up to 1 yr after KT.
In conclusion, this is the first report of successful KT after CR
of APL. This case suggests that KT can be considered in ESRD
patients with APL without a lengthy period of waiting. However,
accumulation of more cases of a similar nature may be required
before definite conclusions can be made.
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