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Browse Specialty Staffing ServicesMortality and Life-threatening outcomes of chemotherapy or Anti-neoplastic drugs in Immunocompromised patients: An overview.
Author: Awais Afzal Mohd Afsar
Introduction:
Immunity is our body’s ability to recognize germs to prevent them from causing illness. Our immune system helps to identify and eliminate dangerous germs that enter the body before they can cause disease or damage. Immunity to a disease is achieved by the presence of antibodies which are proteins produced by the body to neutralize or destroy toxins, pathogens, and other disease-carrying agents, for example Measles Pneumonia or Fungal infections. Antibodies will protect the person who will get in contact with these diseases. Patient’s or host’s defense from infection depends upon a complex and integrated system of physical barriers (like Skin, Lungs, and Body acids), natural immunity (phagocytic cells, natural killer cells, complement) and acquired immunity (B and T lymphocytes) and passive immunity. There are two types of immunity.
Active Immunity: Active Immunity results when exposure to a disease organism triggers the immune system to produce antibodies to that disease. Active immunity can be acquired through natural immunity or vaccine-induced immunity. There are two types of active immunity,
- Natural immunity
- Vaccine-induced immunity
Passive Immunity: Passive immunity is provided when a person is given antibodies to a disease rather than producing them through his or her own immune system. Examples of passive immunity includes Immunity acquires by newborn babies from their mother’s placenta and immunity acquired by the antibody containing blood products such as immune globulin. However, passive immunity lasts only for a few weeks or months. Only active immunity is long-lasting
Immunosuppression: Immunosuppression is a condition in which the body’s immune system and its ability to fight the infectious and other disease get suppressed and the patients with suppressed immune system are called immunocompromised
patients. These patients are more prone to get infectious and other diseases because their ability to fight with infection is severely decreased.
Most of the anti-neoplastic agents or chemotherapeutic agents like alkylating agents such as Cyclophosphamide, azathioprine, chlorambucil, and methotrexate, these are the cytotoxic drugs commonly used for immunosuppression. Any person may have deficiencies of one or more components of host defense, but no one is defenseless. Because each functional compartment of the immune system plays a specialized role in host defense, defects in specific functions lead to increased susceptibility to specific pathogens. This defense might be altered by these drugs or by pre-existing diseases which can results in severe outcomes.
Discussion:
Most of the patients take long-term anti-neoplastic medication for cancer. Cancer patients that are immunosuppressed by the Anti-cancer treatment might be at risk of some serious life-threatening events as outcome which can leads to death. These events include Bacterial infection like pneumonia and tuberculosis, viral infection which includes influenza, HIV which can leads to AIDS, Human papillomavirus (HPV) and most importantly COVID-19. Other adverse events include anemia, retinal detachment, and kidney disorder. Immunosuppressants are also used in GVHD prophylaxis in patients who require cancer related organ transplantation and patients get post transplantation infections due to these drugs which include Acute rejection, Cytomegalovirus (CMV) infection, and Surgical site infections. Abdominal complication and cardiotoxicity can also develop in patients while on Chemotherapeutic drugs. Some examples of immunosuppressive drugs are given below which can be used in cancer treatments,
- Cyclophosphamide
- Rituximab
- Cytarabine
- Methylprednisolone
- Methotrexate
- Etoposide
- Capecitabine
- 5-fluorouracil (5-FU)
- Carmustine and Lomustine
- Ifosfamide
- Carboplatin and Cisplatin
- Oxaliplatin
- Thiotepa
- sirolimus
Sometimes these drugs also interact with COVID-19 vaccine (BNT162B2, Corona Vac, Moderna, and Sputnik V) and decrease their effectiveness. Failure to achieve an antibody response to the COVID-19 vaccine has been reported to be associated with ongoing treatments such as glucocorticoids, mycophenolate mofetil, and rituximab. it was reported that GC, rituximab, and abatacept in combination with MTX and the use of mycophenolate mofetil decreased immunogenicity after vaccination [7].
In this section, we review secondary immunodeficiencies and other compromises in host defenses that result because of treatment with a variety of anti-neoplastic agents. The consequences of treatment for malignancy, of prevention and treatment of allograft rejection, and of the treatment for rheumatologic and autoimmune diseases will be reviewed. Several studies and case reports have reported such scenarios.
Mitoxantrone secondary progressive, progressive relapsing, or worsening relapsing- remitting multiple sclerosis and Cytarabine is a pyrimidine nucleoside analogue used to treat acute non-lymphocytic leukemia, lymphocytic leukemia, and the blast phase of chronic myelocytic leukemia and act through direct DNA damage and incorporation into DNA, Borgstedt-Bendixen et al. included 313 patients from which episode of abdominal pain was associated with death in 5 patients (6%). Four of these patients had accompanying sepsis. The fifth patient received AM under dialysis and died from multiorgan failure without any signs of concurrent sepsis. In Total 27 patients developed 32 episodes of AP associated with infection grade 3 or 4. Six of 313 patients (2%) developed appendicitis, primarily during induction therapy [1]. Etoposide is a podophyllotoxin derivative used to treat testicular and small cell lung tumors. It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Marafioti et al. include 39 Hodgkin Lymphoma patients treated TEAM regimen (including Thiotepa, etoposide and cytarabine and 5 patients underwent maintenance therapy with Brentuximab, Ibrutinib and rituximab. In total 8 patients died; one patient died due to sepsis [2]. Methotrexate is an antineoplastic agent used the treatment of a wide variety of cancers as well as severe psoriasis, severe rheumatoid arthritis, and juvenile rheumatoid arthritis, Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti- inflammatory actions, Cernauskiene et al. present 57 patients with newly diagnosed primary central nervous system lymphoma requiring transplantation. Patients received sequential induction therapy consisting of 4 cycles of Rituximab and high dose cytarabine. The most common complications were infection (26 patients with febrile neutropenia, 9 patients developed bacteremia, 3 pneumonia and 2 Urinary tract infection). There was one treatment- related death caused by sepsis and fungal pneumonia [3]. Harris et al. present a study with 289 patients receiving high dose Cytarabine along with L-Asparaginase for Refractory Acute Lymphoblastic Leukemia There were 10 deaths (19%) during rescue reinduction; four patients died with progressive leukemia with or without concomitant infection or toxicity and six died primarily due to infection or toxicity without evidence of leukemia on biopsy or autopsy (12% regimen-related mortality). One patient died several months after receiving Cytarabine along with L-Asparaginase while in continued remission; death was due to progressive fungal infection acquired during rescue reinduction. Three patients died of toxicity and two of infection shortly after marrow transplant [4]. Ji et al. discussed severe adverse reactions during treatment gestational trophoblastic neoplasia Grade 4 (life-threatening) myelosuppression and neutropenia were significantly more frequent in the FAEV (Floxuridine, actinomycin D, etoposide, and vincristine) group. The occurrences of other grade 4 adverse reactions, including thrombocytopenia, anemia, liver damage, renal damage, vomiting, diarrhea, and oral ulcers [5]. Dexamethasone and Methylprednisolone are glucocorticoids available in various modes of administration that are used for the treatment of various inflammatory conditions, including bronchial asthma, as well as endocrine and rheumatic disorders and sometimes along with chemotherapy. Lonial et al. conducted a study for Iberdomide plus dexamethasone in heavily pretreated late line relapsed or refractory multiple myeloma and 14 (13%) died during the treatment period; of these, seven deaths were disease-progression related, five were due to infection (three related to COVID-19, one abdominal sepsis, and one sepsis) [6]. These drugs like Rituximab and glucocorticoids also reduced the immunogenicity of Vaccines in most of the cases, Furer et al. discussed how mRNA BNTb262 vaccine was immunogenic in most of the patients with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity [7]. Batibay et al reported that five patients taking Rituximab had positive RT-PCR tests for COVID-19 infection after their two doses of vaccination. Only one patient required hospitalization and oxygen support [8]. Ahmed et al. present a case of 52-year-old male who had two episodes of cardiac arrest related to Paclitaxel and pembrolizumab infusion [9].
Conclusion:
This article showed that, how most of the Anti-neoplastic/Chemotherapeutic drugs or Corticosteroids used with chemotherapy in the treatment of cancer affect the patient’s immune system (by acting as immunosuppressant) and make their live vulnerable to various fungal, infectious, and other diseases which can be fatal in most of the cases. Nowadays reports are showing that the patients taking these drugs are more prone to get COVID-19 infection as well as these agents can reduced the immunogenicity of COVID-19 vaccines which is a serious threat to the people’s health. On the other hand, we cannot avoid the use of these drugs as they could be life savior for the Cancer patients so what we can do to avoid these outcomes.
Here are some solutions to this problem. we can use immunotherapy or anti-vascular therapy along with chemotherapy or we can take preventive measures to avoid getting infected by,
- maintaining good hygiene while on treatment,
- limit contact with people (sick people),
- drink safe water practice safe sex,
- And immediately approach a doctor in case of appearance of any sign or symptoms of infection or
- There are some diet guidelines available online to immunosuppressed
- Other preventive measures include frequent blood tests to monitor drug effectiveness and side effects,
- transplant recipients may stop taking the drugs after the risk of GVHD
- In pregnant women some immunosuppressants can cause birth defects while some medicine may be harmful to take during pregnancy or while There will be a need to switch to a different medicine by consulting doctor.
References:
- [1]- Sofie Borgstedt-Bendixen, MD, Jonas Abrahamsson, MD et al. Abdominal Complications During Treatment Abdominal Complications During Treatment: J Pediatr Hematol Oncol Volume 44, Number 5, July 2022
- [2]- Marafioti, S. Di Folca et al. Outcomes of reduced dose TEAM (thiotepa. Etoposide, cytarabine, melphalan) prior to autologous stem cell transplantation for Hodgkin and non- Hodgkin lymphoma: A monocentric experience: Bone Marrow Transplantation (2022) 57:100-416
- [3]- Cernauskiene et al. Outcome of patients with newly diagnosed primary central nervous system lymphoma after sequential high-dose methotrexate, cytarabine, thiotepa based chemoimmunotherapy followed by autologous stem cell transplantation: A monocentric experience: Bone Marrow Transplantation (2022) 57:100-416
- [4]- Richard Harris, MD, Harland N. Sather et al. High-Dose Cytosine Arabinoside and L-Asparaginase in Refractory Acute Lymphoblastic Leukemia: The Children’s Cancer Group Experience: Medical and Pediatric Oncology 30:233–239 (1998)
- [5]- Mingliang Ji, Shiyang Jiang et al. Efficacies of FAEV and EMA/CO regimens as primary treatment for gestational trophoblastic neoplasia: British Journal of Cancer (2022) 127:524 – 530
- [6]- Sagar Lonial, Rakesh Popat et Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial: Lancet Haematol 2022; 9: e822–32
- [7]- Victoria Furer, Tali Eviatar et Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study: Ann Rheum Dis 2021;80:1330–1338. doi:10.1136/annrheumdis-2021-220647
- [8]- Sevilay Batıbay, Rezan Koçak Ulucaköy et Immunogenicity and safety of the CoronaVac and BNT162b2 Covid-19 vaccine in patients with infammatory rheumatic diseases and healthy adults: comparison of diferent vaccines: Infammopharmacology (2022) 30:2089–2096
- [9]- Omar Sh Ahmed Himil Mahadevia et al. A Case of Full Recovery from Prolonged Cardiac Arrest after Infusion with Paclitaxel and Pembrolizumab: Case Rep Oncol 2022; 15:1063–1073: DOI: 1159/000527205