Vo
lu
m
e
5,
Ju
ne
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
A CLINICAL CASE OF ACUTE PROMYELOCYTIC LEUKAEMIA IN A PATIENT
WITH RENAL PATHOLOGY
Almamatov Ortik Ibragimovich,
Samarkand Regional Multidisciplinary Medical Center – Department of Therapy, Therapist.
Fayziyev Akbar Ubaydullo ugli,
Samarkand Regional Multidisciplinary Medical Center – Department of Therapy, Therapist.
Uzakova Oyjamol Narzullaevna
,
Samarkand State Medical University, Department of Hematology, Trainee-Assistant.
Abstract.
Acute promyelocytic leukaemia (APL) is a distinct subtype of acute myeloid
leukaemia characterized by a specific genetic translocation and a high risk of coagulopathy.
The coexistence of APL with renal pathology complicates both diagnosis and treatment,
requiring a tailored multidisciplinary approach. We report a case of a 47-year-old male with
APL complicated by acute kidney injury, presenting with bleeding, pancytopenia, and
disseminated intravascular coagulation. Diagnosis was confirmed by bone marrow
examination and molecular testing for the PML-RARA fusion gene. Treatment included all-
trans retinoic acid and reduced-dose arsenic trioxide, adjusted for renal impairment, along
with supportive care addressing coagulopathy, tumour lysis syndrome prophylaxis, and
infection management. The patient achieved complete hematologic and molecular remission
with restoration of renal function. This case underscores the importance of individualized
therapy and vigilant monitoring in managing APL patients with renal complications,
demonstrating that successful outcomes are achievable despite significant comorbidities.
Key words:
Acute promyelocytic leukaemia; Renal pathology; Acute kidney injury; All-
trans retinoic acid; Arsenic trioxide; Disseminated intravascular coagulation; Molecular
remission; Multidisciplinary management
Introduction
Acute promyelocytic leukaemia (APL) is a distinct and highly aggressive subtype of acute
myeloid leukaemia (AML), characterised by the accumulation of abnormal promyelocytes in
the bone marrow and peripheral blood. APL is defined cytogenetically by the
t(15;17)(q24;q21) translocation, which results in the PML-RARA fusion gene. This
molecular hallmark not only underpins the disease's pathogenesis but also provides a unique
opportunity for targeted therapy, which has significantly improved survival rates in recent
decades. The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has
transformed APL from one of the most fatal forms of leukaemia into one of the most curable
haematological malignancies.
However, the clinical course of APL can be complicated by severe coagulopathy, early
haemorrhagic events, and organ dysfunction, all of which may be life-threatening if not
promptly recognised and managed. Renal pathology—whether pre-existing or secondary to
the disease or its treatment—adds further complexity to diagnosis and therapeutic planning.
Acute kidney injury (AKI) in patients with APL may result from tumour lysis syndrome,
Vo
lu
m
e
5,
Ju
ne
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
sepsis, nephrotoxic drug exposure, or direct leukemic infiltration, significantly impacting
treatment tolerability and overall prognosis.
The management of APL in patients with renal impairment presents a particular challenge,
as the pharmacokinetics and toxicity profiles of ATRA, ATO, and supportive therapies may
be altered. Dose adjustments, careful fluid and electrolyte management, and
multidisciplinary coordination are essential to achieve remission without causing further
renal compromise. Moreover, renal dysfunction can mask early clinical signs of leukaemia,
delay diagnosis, or confound laboratory assessments such as creatinine-based renal function
estimation and drug clearance.
This case report presents the clinical course of a patient diagnosed with acute promyelocytic
leukaemia in the setting of underlying renal pathology. It highlights the diagnostic
challenges, therapeutic modifications, and outcomes observed, and discusses the
implications for clinical practice. Through this case, we aim to contribute to the growing
div of evidence regarding the management of haematological malignancies in patients with
multi-organ comorbidities, particularly renal disease.
Methods
This clinical observation was conducted at the Samarkand Regional Multidisciplinary
Medical Center in early 2025, with informed consent obtained from the patient and approval
granted by the institutional ethics committee. A comprehensive diagnostic and treatment
protocol was applied, integrating haematological and nephrological approaches. Upon
presentation, the patient underwent a complete blood count, peripheral smear analysis,
coagulation tests, and biochemical profiling to assess kidney function, electrolyte balance,
and the severity of cytopenia. Bone marrow aspiration and biopsy were performed, revealing
a predominance of abnormal promyelocytes, while molecular confirmation of the PML-
RARA fusion gene was established through RT-PCR and FISH testing. This enabled a
prompt diagnosis of acute promyelocytic leukaemia. Given the patient's compromised renal
function at baseline, as indicated by elevated creatinine levels and reduced eGFR, careful
adaptation of the therapeutic regimen was necessary. All-trans retinoic acid (ATRA) was
initiated at standard dosing (45 mg/m²/day), while arsenic trioxide (ATO) was introduced
cautiously at 0.10 mg/kg/day with dose modifications based on daily renal monitoring.
Supportive therapy included prophylaxis for tumour lysis syndrome, transfusions of platelets
and fresh frozen plasma to manage coagulopathy, and empiric broad-spectrum antibiotics
during neutropenic episodes. Fluid management and nephrotoxic drug avoidance were
prioritized to prevent further renal deterioration. Treatment was guided by a
multidisciplinary team consisting of haematologists, nephrologists, and intensive care
specialists, who jointly monitored therapy tolerance, complications such as QT interval
prolongation, and infection risk. Continuous documentation of laboratory values, patient
responses, and treatment adjustments provided the clinical framework for analysing this case
and evaluating the outcomes of personalised treatment in a patient with dual haematologic
and renal pathology.
Results
Vo
lu
m
e
5,
Ju
ne
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
The patient, a 47-year-old male, presented with spontaneous mucosal bleeding, fatigue, and
oliguria. Laboratory evaluation revealed pancytopenia: haemoglobin 76 g/L, leukocytes
2.1×10⁹/L, and platelets 18×10⁹/L. The peripheral blood smear showed 65% abnormal
promyelocytes with frequent Auer rods. Coagulation parameters were markedly abnormal—
prothrombin time prolonged, fibrinogen 0.7 g/L, and elevated D-dimer—suggesting
disseminated intravascular coagulation (DIC). Renal assessment showed serum creatinine at
280 µmol/L, blood urea nitrogen of 14 mmol/L, and an estimated glomerular filtration rate
(eGFR) of 28 mL/min/1.73 m², confirming acute renal dysfunction.
Bone marrow aspiration confirmed hypercellularity with >80% promyelocytes, and
cytogenetic analysis identified the t(15;17)(q24;q21) translocation. RT-PCR confirmed the
PML-RARA fusion transcript. Based on these findings, a diagnosis of acute promyelocytic
leukaemia was made in the setting of acute kidney injury (AKI).
ATRA therapy was initiated promptly, and ATO was introduced at a reduced dose due to
renal impairment. The patient was also given prophylactic allopurinol and aggressive
intravenous hydration to prevent tumour lysis syndrome, with careful fluid balance due to
impaired renal excretory function. Platelet and plasma transfusions were administered to
manage ongoing bleeding and correct coagulopathy. On day 4 of treatment, the patient
developed febrile neutropenia, for which broad-spectrum antibiotics were initiated. No
bacterial growth was found in cultures, and fever resolved within 72 hours.
Renal function gradually improved with supportive care; creatinine decreased to 170 µmol/L
by day 14 and normalized (98 µmol/L) by day 25. Haematological response to therapy was
favourable. By day 28, the patient achieved complete remission: bone marrow showed less
than 5% blasts, platelet counts normalized, and peripheral promyelocytes were no longer
detectable. Molecular testing on day 35 showed no detectable PML-RARA transcripts.
Throughout induction therapy, no severe differentiation syndrome or QT prolongation
occurred. The patient tolerated the treatment well after initial adjustments and was
discharged on day 38 with a plan to continue consolidation therapy under close
nephrological monitoring. The outcome demonstrated successful remission of APL
alongside full renal function recovery, indicating the effectiveness of an individualized,
multidisciplinary management approach.
Discussion
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia
characterized by a specific chromosomal translocation t(15;17), resulting in the PML-RARA
fusion gene. This genetic hallmark not only facilitates a targeted therapeutic approach but
also underscores the importance of rapid diagnosis and initiation of treatment due to the
disease’s aggressive clinical course. The coexistence of APL with renal pathology, as
presented in this case, introduces significant challenges in both diagnosis and management,
necessitating careful consideration of therapeutic strategies and supportive care to optimize
outcomes.
The clinical presentation of APL often involves bleeding diatheses resulting from
disseminated intravascular coagulation (DIC), a critical complication observed in up to 80%
Vo
lu
m
e
5,
Ju
ne
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
of cases. In our patient, profound thrombocytopenia and altered coagulation parameters
signaled the presence of severe coagulopathy, complicating the clinical picture. This is
consistent with the pathophysiology of APL, where the release of procoagulant substances
by abnormal promyelocytes triggers systemic activation of the coagulation cascade, leading
to fibrin deposition and consumption of platelets and clotting factors. Prompt recognition
and correction of coagulopathy are vital to reducing morbidity and mortality, as
haemorrhagic events remain a leading cause of early death in APL patients.
Renal dysfunction in APL patients may be multifactorial. It can arise as a consequence of
tumor lysis syndrome, nephrotoxic effects of chemotherapy, infection-related sepsis, or
direct leukemic infiltration. In this case, the patient’s acute kidney injury (AKI) presented a
significant obstacle to standard treatment protocols, necessitating modifications in dosing
and close monitoring to avoid further nephrotoxicity. The reduced dose of arsenic trioxide
(ATO) was critical in minimizing renal adverse effects while maintaining therapeutic
efficacy. This cautious approach highlights the need for individualized treatment regimens
based on comorbid conditions.
The use of all-trans retinoic acid (ATRA) remains a cornerstone in APL therapy, promoting
differentiation of malignant promyelocytes into mature granulocytes. Importantly, ATRA is
generally well tolerated in patients with renal impairment, making it suitable for initial
induction therapy in such complex cases. In contrast, arsenic trioxide, although highly
effective in achieving remission, carries a risk of QT interval prolongation and electrolyte
disturbances, which can be exacerbated by compromised renal clearance. In this patient,
daily renal function monitoring and electrocardiographic surveillance facilitated timely dose
adjustments and prevented severe cardiac toxicity.
Management of tumor lysis syndrome (TLS) is another critical aspect, particularly in
patients with pre-existing renal pathology. Aggressive hydration, uric acid reduction with
allopurinol, and close electrolyte monitoring were integral components of care to prevent
exacerbation of renal injury. The favorable renal recovery observed post-treatment
underscores the effectiveness of these preventive measures.
Infectious complications represent a common challenge during APL treatment due to
profound neutropenia and immunosuppression. The occurrence of febrile neutropenia in this
patient was managed successfully with empiric broad-spectrum antibiotics and careful
supportive care, without progression to sepsis. This outcome reflects the importance of early
recognition and prompt intervention in preventing life-threatening infections.
This case also emphasizes the role of multidisciplinary collaboration in managing patients
with complex comorbidities. The involvement of haematologists, nephrologists, intensivists,
and pharmacists enabled a comprehensive approach that balanced effective leukaemia
treatment with renal protection and supportive management. Such coordinated care is
essential in tailoring therapy, monitoring adverse effects, and improving overall patient
prognosis.
Despite the challenges posed by renal impairment, the patient achieved complete
hematologic and molecular remission, illustrating that with appropriate dose adjustments
and supportive strategies, standard APL treatment protocols can be successfully
Vo
lu
m
e
5,
Ju
ne
,2
02
5
,
M
ED
IC
AL
SC
IE
N
CE
S.
IM
PA
CT
FA
CT
OR
:7
,8
9
implemented. The absence of severe differentiation syndrome, a potentially fatal
complication of ATRA therapy, further contributed to the positive outcome.
Conclusion
In conclusion, this case illustrates the complexity of treating acute promyelocytic leukemia
in the presence of renal dysfunction. It underscores the necessity for early diagnosis,
individualized therapy, vigilant monitoring, and multidisciplinary management to optimize
treatment efficacy and minimize toxicity. Future studies with larger patient cohorts are
needed to establish standardized protocols for managing APL complicated by renal
pathology and to explore novel therapeutic agents with improved safety profiles in this
vulnerable population.
References:
1.
Абдураҳмонов, Б. М., & Усмонов, А. Х. (2020). Клинические особенности и
лечение острого промиелоцитарного лейкоза.
Вестник гематологии
, 12(3), 45-53.
2.
Ахмадов, Р. Т., & Каримова, М. С. (2019). Особенности течения лейкемий у
пациентов с почечной патологией.
Ташкентский медицинский журнал
, 7(2), 112-118.
3.
Döhner, H., Estey, E., Grimwade, D., Amadori, S., Appelbaum, F. R., Büchner, T., ...
& Bloomfield, C. D. (2017). Diagnosis and management of acute myeloid leukemia in
adults: 2017 ELN recommendations from an international expert panel.
Blood
, 129(4), 424-
447. https://doi.org/10.1182/blood-2016-08-733196
4.
Иванова, Н. В., & Петрова, Е. А. (2018). Роль коагулопатий при остром
промиелоцитарном лейкозе.
Российский журнал гематологии
, 14(1), 27-35.
5.
Махмудов, И. Ш., & Юсупова, Л. Б. (2021). Иммунная тромбоцитопения и
почечная недостаточность: клинические аспекты.
Узбекский медицинский журнал
,
3(4), 59-65.
6.
Sanz, M. A., & Fenaux, P. (2019). Management of acute promyelocytic leukemia:
recommendations from an expert panel on behalf of the European LeukemiaNet.
Blood
,
133(15), 1630-1643. https://doi.org/10.1182/blood-2018-11-881040
7.
Shaikh, S., & Hoda, D. (2019). Acute promyelocytic leukemia and renal
complications: clinical challenges and treatment strategies.
Leukemia Research
, 85, 106205.
https://doi.org/10.1016/j.leukres.2019.106205
8.
Тураева, Г. Р., & Абдуллаева, Д. Х. (2022). Особенности лечения лейкемии у
больных с почечной патологией.
Журнал клинической медицины
, 5(2), 99-105.
9.
Умаров, З. М., & Нурматов, А. Р. (2020). Современные подходы к диагностике
и лечению острых лейкемий.
Самаркандский медицинский вестник
, 1(1), 15-22.
10.
World Health Organization. (2016).
Classification of Tumours of Haematopoietic
and Lymphoid Tissues
(Revised 4th edition). Lyon, France: IARC.
11.
Абдиев, К., Махмонов, Л., Мадашева, A., & Маматкулова, Ф. (2021). Business
games in teaching hematology. Общество и инновации, 2(6), 208-214.
12.
Махмудова, А. Д., Жураева, Н. Т., & Мадашева, А. Г. (2022).
НАСЛЕДСТВЕННЫЙ ДЕФИЦИТ ФАКТОРА СВЕРТЫВАНИЯ КРОВИ Х-БОЛЕЗНЬ
СТЮАРТА-ПРАУЭРА. Биология, 4, 137.
13.
Madasheva, A. G., Yusupova, D. M., & Abdullaeva, A. A. EARLY DIAGNOSIS
OF HEMOPHILIA A IN A FAMILY POLYCLINIC AND THE ORGANIZATION OF
MEDICAL CARE. УЧЕНЫЙ XXI ВЕКА, 37.
