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Table of Contents
Year : 2022  |  Volume : 19  |  Issue : 2  |  Page : 307-309

Hypersensitivity reactions to liposomal amphotericin in a bone marrow transplant patient

1 Specialized Bone Marrow Transplant Center, Medical City Complex, Baghdad, Iraq; School of Pharmaceutical Sciences, University of Sains Malaysia, Gelugor, Penang, Malaysia
2 Specialized Bone Marrow Transplant Center, Medical City Complex, Baghdad, Iraq

Date of Submission06-May-2022
Date of Acceptance19-May-2022
Date of Web Publication30-Jun-2022

Correspondence Address:
Alaa Hussein Alsajri
Specialized Bone Marrow Transplant Center, Medical City Complex, Baghdad, Iraq; School of Pharmaceutical Sciences, University of Sains, Malaysia, Gelugor, Penang
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/MJBL.MJBL_67_22

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Introduction: Hodgkin’s lymphoma is one of the treatable types of blood cancer. Autologous bone marrow transplantation is used as one way to treat this disease. Neutropenic fevers are treated with antibiotics and antifungals, including amphotericin B. Adverse effects and hypersensitivity to liposomal amphotericin, Ambisome, are very uncommon compared with conventional amphotericin. Case Report: In this case, we noticed hypersensitivity reactions to the Ambisome, represented by an increase in body temperature, a drop in blood pressure, and hypo-oxygenemia, in addition to an increase in the heart rate. Case Management: The patient was treated with injections of hydrocortisone, chlorpheniramine, and normal saline, in addition to giving oxygen; he was improved. Conclusion: In spite of the few cases that have recorded hypersensitivity reactions to the Ambisome, it is necessary to conduct an allergy test and to monitor the patient well when giving the Ambisome, especially in the first dose.

Keywords: Ambisome, drug allergy, drug safety, infectious disease, liposomal amphotericin, therapeutic drug monitoring

How to cite this article:
Alsajri AH, Al-Hishma SW, Abbas Shubber M. Hypersensitivity reactions to liposomal amphotericin in a bone marrow transplant patient. Med J Babylon 2022;19:307-9

How to cite this URL:
Alsajri AH, Al-Hishma SW, Abbas Shubber M. Hypersensitivity reactions to liposomal amphotericin in a bone marrow transplant patient. Med J Babylon [serial online] 2022 [cited 2022 Dec 7];19:307-9. Available from: https://www.medjbabylon.org/text.asp?2022/19/2/307/349492

  Introduction Top

Bone marrow transplant, known as hematopoietic stem cells transplant (HSCT), entails the infusion of healthy hematopoietic stem cells into patients with diseased or dysfunctional bone marrow. This aims to boost bone marrow function and allows to either destroy malignant tumor cells or generate functional cells that can replace the dysfunctional cells.[1] It can be used in various types of diseases including leukemia, lymphoproliferative disorders, solid tumor, nonmalignant disorders, and others.[2] Life-enhancing HSCT is mainly divided into two main types: the autologous form (stem cells are harvested from the recipient) and the allogeneic form (stem cells are harvested from a different donor individual or from cord blood units).[3]

Our bone marrow transplant center is at the medical city, Baghdad. We commonly use autologous stem cell transplant as a mainstay treatment line for patients with relapsed Hodgkin lymphoma, moderate–high degree non-Hodgkin lymphoma, and multiple myeloma after the failure of therapy with chemotherapy alone or in combination with radiotherapy. Patients who undergo bone marrow transplantation procedures are at high risk of severe illness, infectious complications, and myelosuppression including neutropenia.[4]

Low neutrophil count (less than 500/μL) and febrile, 38°C, that consist for 1 h or 38.3°C for one reading and few days after transplantation have febrile neutropenia are considered as a medical emergency. It may represent the only clinical sign of severe infection leading to the increased length of hospital admission and prompt the physician to initiate empirical broad spectrum antimicrobial therapy prior to the isolation of bacterial organism. Early administration of antimicrobial will improve overall morbidity and mortality rates.[5] Choosing appropriate empirical therapy is a raising challenge especially in an era of elevated antimicrobial resistance rates.[6] Unresponsiveness with persistent or recurrent fever despite antibiotic therapy could indicate an invasive fungal infection that requires the administration of empirical antifungal therapy because an invasive fungal infection risk increases with neutropenia duration and severity.[7],[8] Amphotericin B deoxycholate (conventional) acts through the pore formation at the fungal cell membrane, and for many decades is believed to be a cornerstone treatment of fungal infection.[9] Unfortunately, empirical treatment with conventional amphotericin B is limited by breakthrough fungal infections, acute toxic effects related to the infusion, and dose-limiting nephrotoxic reactions.[10] An alternative strategy that improves outcomes such as evaluating lipid formulations of amphotericin to enhance tolerability profile conventionally has demonstrated significant benefits in treating fungal infections such as liposomal amphotericin B.[11] In our bone marrow transplant center, we started to administer liposomal amphotericin, which is a unique lipid formulation of amphotericin B used for a wide range of medically fungal pathogens. It has significantly improved safety and toxicity profile compared with conventional amphotericin B deoxycholate.[12]

  Case Details Top

An 18-year-old man diagnosed with Hodgkin’s lymphoma was admitted to the Specialized Center for Bone Marrow Transplantation for autologous stem cell transplantation.

The LEAM (lomustine, cytarabine, etoposide, and melphalan) therapeutic protocol was used as a conditioning regimen before the stem cell transplantation according to the National Health Service protocol.[13]

Three days after the stem cell transplantation (day +4), the patient entered a state of low neutrophil count, which was equal to 35 μL. On the next day (day +5), the patient’s temperature elevated to 38°C, which was considered as neutropenic fever. The doctor began dispensing antibiotics to the patient, such as piperacillin + tazobactam, and then meropenem, but the temperature did not decrease. The doctor added vancomycin treatment in order to cover the gram-positive bacteria; then he added amikacin, but to no benefit. On the eighth day after the cell transplantation (day +9), the doctor added the liposomal amphotericin (Ambisome) therapy in order to control the neutropenic fever. The dose of Ambisome was calculated on the basis of the patient’s weight,[10] which was compromising 70 kg, 210 mg of Ambisome in 500 mL of glucose-water 5% (D5W) infused over 2 h. As a liposomal amphotericin is safer than conventional amphotericin, the treatment of Ambisome was given without sensitivity test or the addition of hydrocortisone and chlorpheniramine before it.[14]

After completing the infusion of the Ambisome, the patient suffered from skin rash, redness, and chills accompanied by the elevation in body temperature, increased pulse rate, a drop in blood pressure, and a decrease in the percentage of blood saturation with oxygen, as shown in [Table 1]. In order to ascertain the possibility that the drug is the cause of hypersensitivity, the Naranjo score was calculated and it was equal to 5. This indicates that the drug caused the hypersensitivity reaction type 1.[15]
Table 1: Vital signs before, at the end of infusion, and after Ambisome administration

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The physicians prescribed hydrocortisone vial 100 mg plus chlorpheniramine ampoule, normal saline 0.9%, and oxygen therapy to manage the patient’s severe allergy. After the rapid intervention, the patient’s condition was clinically stable.

  Discussion Top

Hodgkin’s lymphoma is a type of blood cancer that responds to the treatment. This type of disease is considered uncommon. Chemotherapy is the first line in controlling this disease. In the advanced stages of the disease and in recurrent cases, a bone marrow transplant may be performed to control the disease.[16]

In general, marrow transplantation is divided into two main types according to the source of stem cells, which are autologous bone marrow transplantation where stem cells from the patient, and allogeneic bone marrow transplantation, from a donor. There are many chemotherapeutic protocols prior to the marrow transplantation, in order to prepare the bone to receive stem cells. These chemical protocols are in high doses and cause many complications, including neutropenia and neutropenic fever.[17]

One of the treatments used in the treatment of neutropenic fever is the liposomal amphotericin B (Ambisome).[9]

A hypersensitivity reaction to liposomal amphotericin has been reported in many cases.[18],[19],[20],[21],[22] This is the first case to report hypersensitivity to liposomal amphotericin B (Ambisome) in patients with bone marrow transplantation in the bone marrow transplant center, Iraq. The allergy occurred from the first dose that was given to the patient, and the situation was corrected by giving some medications that reduced the sensitivity and improved the patient’s condition. Although this is the first case of an allergic reaction to liposomal amphotericin B recorded in our center, great care must be taken in patients who take liposomal amphotericin B, especially in the first dose.

The approval of the bone marrow transplant center and of the patient was obtained in order to publish this data and study.

Ethical approval

The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki. It was carried out with patients’ verbal and analytical approval before the sample was taken. The study protocol and the subject information and consent form were reviewed and approved by a local ethics committee according to the document number 7 in April 26, 2022.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Khaddour K, Hana CK, Mewawalla P Hematopoietic stem cell transplantation. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing;2021.  Back to cited text no. 1
Gratwohl A, Baldomero H, Aljurf M, Pasquini MC, Bouzas LF, Yoshimi A, et al; Worldwide Network of Blood and Marrow Transplantation. Hematopoietic stem cell transplantation: A global perspective. JAMA 2010;303:1617-24.  Back to cited text no. 2
Bazinet A, Popradi G A general practitioner’s guide to hematopoietic stem-cell transplantation. Curr Oncol 2019;26:187-91.  Back to cited text no. 3
Finefrock D, Varughese T, Ding J, Sanders A, Hewitt K Process for delivering timely antibiotics to febrile bone marrow transplant patients in the emergency department. JCO Oncol Pract 2021;17:e1375-81.  Back to cited text no. 4
Kyriacou DN, Jovanovic B, Frankfurt O Timing of initial antibiotic treatment for febrile neutropenia in the emergency department: The need for evidence-based guidelines. J Natl Compr Canc Netw 2014;12:1569-73.  Back to cited text no. 5
Lin MY, Weinstein RA, Hota B Delay of active antimicrobial therapy and mortality among patients with bacteremia: Impact of severe neutropenia. Antimicrob Agents Chemother 2008;52:3188-94.  Back to cited text no. 6
Michallet M, Ito JI Approaches to the management of invasive fungal infections in hematologic malignancy and hematopoietic cell transplantation. J Clin Oncol 2009;27:3398-409.  Back to cited text no. 7
Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, et al. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: A randomized, controlled trial. Clin Infect Dis 2009;48:1042-51.  Back to cited text no. 8
Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, et al Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med 1999;340:764-71.  Back to cited text no. 9
Moen MD, Lyseng-Williamson KA, Scott LJ Liposomal amphotericin B: A review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs 2009;69:361-92.  Back to cited text no. 10
Cornely OA Aspergillus to zygomycetes: Causes, risk factors, prevention, and treatment of invasive fungal infections. Infection 2008;36:296-313.  Back to cited text no. 11
Stone NR, Bicanic T, Salim R, Hope W Liposomal amphotericin B (Ambisome(®)): A review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs 2016;76:485-500.  Back to cited text no. 12
Kelsey P, Pearce R, Perry J, Kirkland K, Paul R, Lambert J, et al. Substituting carmustine for lomustine is safe and effective in the treatment of relapsed or refractory lymphoma—A retrospective study from the BSBMT (BEAM versus LEAM). Bone Marrow Transplant 2021;56:730-2.  Back to cited text no. 13
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Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 15
Küppers R, Engert A, Hansmann ML Hodgkin lymphoma. J Clin Invest 2012;122:3439-47.  Back to cited text no. 16
Willasch AM, Peters C, Sedláček P, Dalle JH, Kitra-Roussou V, Yesilipek A, et al; EBMT Paediatric Diseases Working Party. Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study. Bone Marrow Transplant 2020;55:1540-51.  Back to cited text no. 17
Cagnoni PJ Liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients. J Antimicrob Chemother 2002;49(suppl 1):81-6.  Back to cited text no. 18
Mukhtar M, Aboud M, Kheir M, Bakhiet S, Abdullah N, Ali A, et al. First report on Ambisome-associated allergic reaction in two Sudanese leishmaniasis patients. Am J Trop Med Hyg 2011;85: 644-5.  Back to cited text no. 19
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