Anorectal Complications in Acute Leukaemia: A retrospective analysis of clinical characteristics, management and outcomes in a tertiary care setting in Oman

Summary

Objectives:

Anorectal complications are common and serious issues among patients with haematological malignancies, leading to significant morbidity and mortality. Limited data are available on their incidence, microbiology screening and management. This study aimed to improve the understanding of these complications in patients diagnosed with acute leukaemia in Oman.

Methods:

This retrospective study was conducted at Sultan Qaboos University Hospital, Muscat, Oman and included patients diagnosed with acute leukaemia who developed anorectal complications over the past decade (2015–2024).

Results:

A total of 100 patients were included in this study; 50% had acute myeloid leukaemia (AML), 35% had acute lymphoblastic leukaemia (ALL) and 36% were newly diagnosed. Of the 119 anorectal complications, fissures were the most common (n = 48/119). Only 19 patients had culture-proven anorectal infections, most commonly caused by Pseudomonas. Both the Surgery and Infectious Diseases teams were involved in management, especially for abscesses. The majority of patients were treated with meropenem (n = 44/176) and metronidazole (n = 39/176). The recurrence rate was 40% and found to be higher among AML patients. A total of 16% of the patients died within 30 days of diagnosing anorectal complications. But their mortality was indirectly related to the anorectal complications.

Conclusion:

Anorectal complications were prevalent among these patients, particularly in those with AML and were more common among newly diagnosed individuals. Fissures were the most frequently observed complication, while abscesses posed the most significant management challenge, requiring collaboration between Surgery and Infectious Diseases teams. Close monitoring of patients can facilitate early detection and intervention of these complications.

Advances in Knowledge

• The majority of patients were newly diagnosed with acute leukaemia and were not started on chemotherapy.

• Fissures were the most frequently observed complications, while abscesses posed the most significant management challenge.

• Most of the anorectal abscesses were caused by Pseudomonas.

• The majority of patients were treated with meropenem and metronidazole.

• Higher recurrences of anorectal complications were observed among patients with a history of fistula, and those patients with active or relapsed disease.

• Acute myeloid leukaemia patients who developed anorectal complications had a higher 1-year mortality rate.

Application to Patient Care

• Most anorectal complications were diagnosed in patients admitted for chemotherapy or when they were experiencing febrile neutropenia, mostly post-chemotherapy sessions.

• Abscesses appeared to be the most common complication requiring multidisciplinary management.

• Referral to Surgical or Infectious Diseases teams showed no significant difference in 30-day mortality, but surgical referral significantly reduced 1-year mortality.

• Intensive cytarabine-containing chemotherapy was a risk factor for the recurrence of the anorectal complications.

• Close monitoring of patients can facilitate early detection and intervention of these complications.

1. Introduction

Anorectal diseases are common and serious complications among patients with haematological malignancies receiving chemotherapy. It can impair the patient's overall quality of life due to the associated pain and discomfort. It can also affect the treatment plan, impacting the timing of therapy initiation.^1,2,3 It is usually characterised by constipation, swelling and severe pain and can cause life-threatening sepsis. Recurrence of these complications is frequent with each subsequent chemotherapy regimen, but their clinical characteristics are underreported in the currently available literature. This impacts the establishment of an optimum approach to guiding clinicians in managing such complications.^1,2,3

Therefore, this study aimed to assess the clinical features of anorectal complications in patients with acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in Oman. Additionally, it described the management and outcomes of these complications.

2. Methods

This retrospective observational study included patients diagnosed with AML or ALL who developed anorectal complications during their admission at Sultan Qaboos University Hospital (SQUH). Specifically, hospitalised patients aged ≥13 years old, diagnosed with acute leukaemia and who presented/or developed any form of anorectal complications in the past 10 years (2015–2024) were included. Patients with chronic anorectal complications before acute leukaemia diagnosis were excluded.

Data were extracted using their medical records (TrakCare, InterSystems Corporation, Boston, Massachusetts, USA) including patients' demographics, details of the haematological malignancies and management plan, type of anorectal complications, symptoms, recurrence, microbiology results and management of the complications.

Anorectal complications encompass various conditions affecting the area around the anus and rectum, including fissures (small tears in the anal canal), fistulas (skin openings near the anus that may lead into a blind pouch or connect through a tunnel to the rectal canal), abscesses (localised collection of fluid presenting as erythematous, firm or fluctuant tender masses around the anus) and haemorrhoids (swelling and inflammation of veins situated around the anus or in the lower rectum).

All admitted patients with acute leukaemia at SQUH undergo weekly swabs from different body areas, including the perianal area.

Descriptive statistics were used to describe the data. Categorical variables were presented as percentages and differences were analysed using the Chi-square test and Fisher's exact test for expected cells of <5. Continuous variables were presented as medians. Multivariable logistic regression was used to determine the association between the risk factors and the recurrence of anorectal complications. An a priori 2-tailed level of significance was set at 0.05. Data was analysed using STATA, (STATA Corporation, College Station, Texas, USA), Version 18.1.

3. Results

Among all patients admitted with acute leukaemia over the past decade, a total of 100 patients developed documented anorectal complications. The median age was 38 years (range: 13–84 years) with the majority being males (61%). The patient cohort included both AML and ALL, with prevalences of 50% and 35%, respectively. Regarding transplantation status, 81% had never undergone transplantation, 16% had received a transplant once and 3% had undergone 2 transplants [Table 1].

Table 1.

Characteristics of patients diagnosed with acute leukaemia who developed anorectal complications from 2015–2024 (N = 100).

Variable	n
Median age in years (range)	38 (13–84)
Gender
Male	61
Female	39
Comorbidities
DM	24
HTN	23
Dyslipidaemia	9
Haematological malignancy
AML	50
ALL	35
APML	11
MPAL	4
Survival
Alive	53
30-day mortality	16
1-year mortality	42
Cause of death (n = 47)
Septic shock	18
Sepsis	9
Febrile neutropenia	5
Disease itself	4
Others	11
Median CBC
Haemoglobin in g/dL	7.95
Platelet	23
WBC	0.8
ANC	0
Median body temperature in °C	37
Median CRP	52.5

DM = diabetes mellitus; HTN = hypertension; AML = acute myeloblastic leukaemia; ALL = acute lymphoblastic leukaemia; APML = acute promyelocytic leukaemia; MPAL = mixed phenotype acute leukaemia; CBC = complete cell count; WBC = white blood cell; ANC = absolute neutrophil count; CRP = c-reactive protein.

Out of the 100 patients, 36% were newly diagnosed with acute leukaemia and 32% had an active disease; 13% of the patients were not initiated on any treatment or chemotherapy at the time of admission due to anorectal complications, while 11% were receiving FLAG-IDA therapy. The majority of the patients (49%) were admitted for chemotherapy, with febrile neutropenia (12%) being the second most common reason for admission. Additionally, 13% of the patients had a concurrent fungal infection.

A total of 119 anorectal complications were reported among the patients, including fissures, fistulas, abscesses and haemorrhoids. Out of 100 patients, 17 had more than 1 complication. The most common complication was fissure, accounting for 48 cases, followed by fistulas and abscesses, each representing 18.5% (n = 22/119) of the cases. The remaining complications were haemorrhoids (n = 18/119) and ulcers (n = 9/119). These complications were often associated with severe local pain (n = 93/100), constipation (n = 46/100) and active rectal bleeding (n = 37/100). Other symptoms experienced by some patients included swelling (n = 21/100), diarrhoea (n = 16/100) and discharge (n = 9/100). Out of the 48 patients with fissures, 45 experienced severe anorectal pain. Among those with fistula and abscess, 21 reported pain. Half of the patients with fissures were constipated and 41.7% (n = 20/48) had active rectal bleeding. The rectal bleeding was less common among patients with abscesses (n = 2/22; P = 0.002).

Out of 100 patients, 19 had culture-proven anorectal infections. The most causative organism was Pseudomonas, identified in 9 out of 21 positive cultures, followed by Klebsiella in 4 cases and E. coli in 3 cases; 6 cultures were polymicrobial. Most positive cultures were obtained from patients with abscesses (n = 12/19; P <0.01). Out of the 48 patients with fissures, 89.6 % had negative cultures while only 10.4 % had positive cultures (5 versus 43 patients; P <0.05). Among the isolated bacteria, 5 were multi-drug resistant (MDR), including 2 NDM Klebsiella, 1 ESBL E. coli, 1 MDR Pseudomonas and 1 carbapenems-resistant Enterococcus.

A total of 83 patients with anorectal complications were referred to and seen by the Surgery team, resulting in 11 surgical interventions, including incision and drainage/or debridement (I/D) and diverting colostomy. Surgical procedures were delayed in 6 patients due to neutropenia. Among patients with abscesses, 95.5% were referred to the Surgery team (P <0.01).

The Infectious Diseases team was involved in only 42% of the patients. The majority of the patients with abscesses were referred (90.9%; P <0.01). Referral to the Infectious Diseases team was more common in patients with positive microbial culture (79.0% versus 21.1%; P <0.01). A total of 176 different antibiotics were prescribed during patients' admission for anorectal complications. Meropenem (n = 44/176) and metronidazole (n = 39/176) were the most commonly used antibiotics among the patients.

The recurrence of the same form of anorectal complications or any other form reached 40% among the patients. Both males and females had an equal chance for recurrence (44.3% and 33.3%, respectively; P >0.05). Almost 64% of the patients with fistulas had recurrence of any form of anorectal complications during the study period (63.6% versus 36.4%; P <0.05). However, only 3 patients with haemorrhoids developed another subsequent form of these complications in the 10-year period (3 versus 15 patients; P <0.05).

A total of 52% of AML patients presented again with anorectal complications during their subsequent admissions to the hospital (52% versus 48%; P <0.05). But only 7 (out of 35 ALL patients) had anorectal complications again (7 versus 28 patients; P <0.05). The risk of recurrence was similar among patients referred to and seen by the Surgery or Infectious Diseases team compared to those who were not; it was higher among patients who had active disease (17 versus 15; P <0.01) and those with relapsed disease (10 versus 6; P <0.01). Out of 36 patients with newly diagnosed leukaemia, 5 of them developed the complication again during the study period (5 versus 31 patients; P <0.01).

There was a statistically significant association between recurrence of anorectal complications and disease status (P = 0.002) and presence of fistula (P = 0.031).

During this 10-year study, approximately 53% of patients remained alive; the 1-year mortality was 42% with 16% dying within 30 days of anorectal complications. The leading causes of death were sepsis (n = 9/47) and septic shock (n = 18/47). Notably, 54% of AML patients died within the same year (P <0.05). Referral to Surgical or Infectious Diseases teams showed no significant difference in 30-day mortality, but surgical referral significantly reduced 1-year mortality (35.4% versus 64.6%; P <0.01). Over half (57.1%) of the patients seen by the Infectious Diseases specialists died within 1 year (P <0.05).

4. Discussion

Anorectal complications are common among patients with haematological malignancies, with reported incidences of 5–9%.^4,5 Patients with acute leukaemia have an increasing incidence of these complications, ranging from 6 to 16.8%.^6,7 In the current study, a total of 100 hospitalised adult patients were documented to have anorectal complications over the past decade. Its incidence and recurrence among patients with AML were higher compared to ALL, and more likely to occur in newly diagnosed individuals. It is often diagnosed in patients admitted for chemotherapy or when they are having febrile neutropenia, mostly post-chemotherapy sessions. Fissure is the most common type of anorectal complication found in these patients.

These complications were significant among male patients (61%) with AML (50%). This aligns with previous studies indicating a greater incidence in males and AML patients; some earlier studies also included other haematological malignancies such as lymphomas and multiple myeloma.^1,6,7,8,9,10 Patients in this study had a median age of 38 years, younger than previously reported ranges of 41–56 years.^1,7,8,10 The majority of the patients were newly diagnosed patients or those with active disease, as previously reported.^7,9

In the current study, the incidence of fissures exceeded that of both fistulas and abscesses, accounting for 40% of total anorectal complications. In previous studies, abscesses, fistulas and haemorrhoids were more common.^1,11,12 The incidence of both abscesses and fistulas was equal at 18.5% in the current study. Notably, approximately one-third of abscesses can progress to fistulas, a chronic condition.¹³ One study reported more abscess formation in younger patients.¹ However, the current study reported no correlation between patient age and type of complication.

Diagnosing anorectal complications in haematological malignancy patients, especially during neutropenia, is challenging.⁷ Immunosuppression can mask symptoms and rectal examinations are often avoided in neutropenic patients.^8,14 Magnetic resonance imaging is considered the most accurate diagnostic tool for these conditions, with approximately 90% accuracy.⁶

Local pain, constipation and rectal bleeding were common features of anorectal complications in this study's patients. However, tenderness, redness, swelling, pain and fever were frequently observed in other studies.¹⁵ This difference is explained by the higher incidence of fissures in this study, which are significantly associated with severe local pain, constipation and bleeding.

The pathogenesis of these complications in acute leukaemia patients remains not entirely understood and is believed to be multifactorial. Neutropenia is a crucial factor in the development of anorectal complications. Most of the patients who developed these complications had a median absolute neutrophil count of 0. Neutropenia is a result of the disease itself or chemotherapy.⁴ It makes the patient more vulnerable to any infection, particularly during the nadir period (1–2 weeks following the administration of chemotherapy).⁹ The degree of neutropenia is also defined by the immunosuppressive potency of the treatment. For example, intensive cytarabine-containing chemotherapy used in AML patients may cause increased severity of neutropenia and mucositis, explaining the higher incidence and recurrence in these patients.^1,4,11 Also, a direct mucosal injury, inflammation and necrosis induced by the cytotoxic medications and accompanied by delayed regeneration of the epithelial cells is a predisposing factor. The cytotoxic chemotherapy may induce indirect injury through the resultant constipation and hard stools, causing repetitive trauma to the mucosa. Constipation can be aggravated by the use of opioid painkillers in these patients. It is also a result of improper diet and fluid intake.^4,9 Apart from constipation, prolonged diarrhoea was shown to be an independent predictor for these complications.¹⁶ In this study, 16% of the patients had diarrhoea.

Out of the 100 patients, only 19 developed infected anorectal disease with a positive culture. Fissures were the most common type found in these patients and they were significantly associated with a lower rate of positive cultures compared to abscesses and other complications. A good understanding of the microbiological profile of these infections is essential for the effective management of patients with acute leukaemia. Most of the infected anorectal complications, mainly abscesses, are caused by gram-negative bacteria, consistent with previous studies.¹ The most common causative organism is Pseudomonas, followed by Klebsiella and E. coli. However, some studies found that E. coli is the most frequently isolated bacteria.^1,12 In general, intestinal flora and other bacteria originating from the gastrointestinal tract, such as Klebsiella and E. coli, are believed to play a significant role in anorectal infections. Chemotherapy and radiotherapy can damage the mucosa, which normally acts as the first barrier against microorganisms. This damage allows organisms from the skin and gastrointestinal cavity to invade and cause infection.^1,11 Patients with acute leukaemia are often admitted to hospitals more frequently and may stay longer due to various complications. Pseudomonas is a significant pathogen causing infections in hospitalised patients, especially those with risk factors such as frequent antibiotic use, advanced age, immunocompromised status and invasive devices.¹⁷

All patients with acute leukaemia admitted to SQUH are swabbed every week from different body areas, including the perianal area, as part of infection control. This practice is also supported by Gallardo-Pizarro et al.'s findings that evaluated the routine weekly surveillance (rectal swabs) among patients with haematological malignancies.¹⁸ They found that 27.5% of patients with positive swabs were colonised with MDR-gram-negative bacteria, mainly E. coli, Klebsiella and Pseudomonas. Furthermore, 38.5% of the colonised patients developed subsequent bloodstream infections with the same organism. The high rate of colonisation is explained by the altered gut microbiome in these patients, leading to the absence of proper immune homeostasis and mucosal integrity.⁴ The study highlighted the increased colonisation by MDR organisms from rectal swabs and the increased risk of infections among the patients and it encourages this practice for early identification of colonisation before the infection develops.¹⁸

Managing a patient with anorectal complications requires collaboration between the Haematology team and other teams such as Surgery and Infectious Diseases.¹³ In the current study, the majority of patients with abscesses were referred to and seen by the Surgery team (95.5%). Surgical intervention posed a challenge for patients managing their anorectal complications due to persistent neutropenia and an increased tendency for bleeding. Out of the 119 anorectal complications, only 11 surgical interventions were performed and 6 had to be postponed. Because of higher incidences of abscesses in previous studies, 20–34% of patients with anorectal diseases underwent surgery by the Surgery team.^1,11 Abscesses I/D was the sole intervention performed by the Surgery team, consistent with previous studies.^11,19 Some evidence supports early surgical intervention for any abscess in leukaemia patients to eliminate the infection source and enable quicker neutrophil recovery. However, surgical intervention remains limited by the patient's neutropenia and thrombocytopenia.^10,11 Some studies have shown better outcomes with surgical interventions in anorectal diseases, while others reported no improvement in patients' outcomes.^2,19 Among the reports, postoperative complications were reported 23.1% of patients in one study and were a direct cause of death in 2.6% of the patients.⁶ The reported mortality was even higher, accounting for 44.4% of patients who underwent, in particular, operative drainage.²⁰ Another study found that 42% of the patients were treated successfully without any need for surgical intervention.²¹

Less than half of the current patients with anorectal diseases were assessed by the Infectious Diseases team. Most of the patients with abscesses required multidisciplinary management. Since abscesses are usually associated with positive cultures, the Infectious Diseases team was consulted about antimicrobials. Combining antimicrobials with surgical intervention is highly recommended for effective abscesses management.²² However, surgical intervention is not possible for some patients, so optimising the antimicrobial selection by the Infectious Diseases team is necessary to help these patients.

Selecting empiric antimicrobial therapy among patients with acute leukaemia is a challenge in view of a higher prevalence of MDR-gram-negative bacteria infections. Any inadequate therapy is linked to higher mortality among the patients.¹⁸ In the current study, a total of 176 antibiotics were prescribed with diverse patterns of use, similar to the observations from a study by Chen et al.¹ Carbapenems, specifically meropenem, were the most commonly prescribed antibiotics (n = 44/176), consistent with previous research.¹ Meropenem is a broad-spectrum antibiotic that targets a range of bacteria, including some MDR bacteria. Some cultures in this study and previous ones were polymicrobial (n = 6/19), highlighting the importance of empirical broad-spectrum antibiotics in suspected anorectal infection. Additionally, 39 patients were receiving metronidazole for their anorectal conditions. Anaerobes such as bacteroides species are potential causative organisms in both current and previous studies and adding metronidazole is therefore recommended.^1,15 Other conservative treatments included painkillers and topical ointments to reduce pain and promote healing. Conservative measures included a sitz bath, which proved to be effective in alleviating symptoms and inflammation.¹⁵

There was a significant rate of recurrence among patients (40%), which was higher compared to 31% reported in a tertiary hospital in Taiwan.¹ Like other studies, AML patients had a higher chance of recurrence than ALL patients. As mentioned previously, this could be explained by the intensive cytarabine-containing chemotherapy. In the current study, most patients were receiving cytarabine-based treatment.^1,11 According to a study by Chang et al., patients with a history of anorectal complications (mainly abscess) have a 10 times higher risk of recurrence with each subsequent chemotherapy and surgical intervention did not reduce the risk.³

The reported mortality rate in earlier studies ranged from 11–57% and was higher among patients with septic complications.^6,11,19 In the current study, 16% of the patients admitted with anorectal complications died within 30 days, which aligns with another study that reported a mortality rate of 14.3% and that anorectal complications were not the direct cause.³ The 1-year mortality rate was 42% and was higher among AML patients. Patients managed by the Surgery team experienced a lower mortality rate. Nevertheless, most patients referred to Infectious Diseases had more severe and complicated anorectal infections, and therefore, more than half of them died within the same year of the complication.

This study was the first regional research to provide insight into anorectal complications among patients with acute leukaemia. It included a larger number of patients compared to the previous studies. The study examined the clinical characteristics of various anorectal complications, microbiology profiles, management and clinical outcomes. Nevertheless, the findings were limited by the retrospective design and the inclusion of only a single tertiary hospital. However, this hospital treats the largest number of patients diagnosed with and treated for acute leukaemia in Oman. Also, fitter patients may be more likely to undergo surgery. Therefore, a larger sample is needed to prove the role of Surgery involvement in reducing 1-year mortality.

5. Conclusion

This study found that anorectal complications affect a significant proportion of patients with acute leukaemia, particularly those with AML, newly diagnosed cases and during post-chemotherapy neutropenia; fissures emerged as the predominant complication in this cohort alongside notable recurrence rates. While conservative treatments predominated due to neutropenia and bleeding risks, surgical interventions for abscesses and optimised antimicrobial therapy targeting MDR gram-negative pathogens such as Pseudomonas showed potential benefits, though outcomes varied with higher mortality in severe cases. Further research is needed to explore these complications in a larger group of patients and among those with different cytogenetic risks.

Authors' Contribution

Najwa Al Himali: Conceptualization, methodology, formal analysis, writing-original draft. Murtadha Al Khabori: Validation, writing-review & editing. Mohamed Al Huneini: Supervision.

Ethics Statement

Ethical approval of this study from the Medical Research and Ethics Committee (MREC #2875). The study was also performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Since personal identification information was marked prior to the analysis, informed consent was not sought.

Conflict of Interest

The authors declare no conflicts of interest.

Funding

No funding was received for this study.

Data Availability

Data is available upon reasonable request from the corresponding author.