According to the World Health Organization, “Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). It is a major global health problem. It can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer.”

WHO estimates that 296 million people were living with chronic hepatitis B infection in 2019, with 1.5 million new infections each year. World Hepatitis Day takes place every year on 28th July to bring the world together under a single theme to raise awareness of the global burden of hepatitis especially with more focus on viral hepatitis and to influence real change.

To discuss the same we had a panel of experts: Dr Anil Arora, Head of Gastroenterology Dept, Sir Gangaram Hospital; Dr. Sanjiv Saigal, Principal Director, Liver and Hepatology, from Max Chain of Hospitals; Dr Sudeep Khanna, Senior Consultant, Gastroenterology Dept, Apollo Chain of Hospitals.

Question: Dr. Saigal, why is hepatitis such a crucial problem? According to WHO reports a person dies of Hepatitis dies every 30 second.

Dr. Sanjiv Saigal: Hepatitis is a huge burden in our country as it is worldwide. Hepatitis basically means inflammation of the liver ad the prime reason for this are the hepatitis viruses which are of four types primarily: Hepatitis A, Hepatitis B, Hepatitis C, Hepatitis D. Hepatitis A & B are self-limiting and spread through blood, water or any fluid. But Hepatitis C & D are huge burden in our country and spread through parental fluid. In India, Hepatitis B has a prevalence of 2-7% and Hepatitis C is 0.5-1.5%. They constitute a huge number if patients in the county and are very important cause of liver related deaths in the country. They also cause liver failure, liver cancer and so on. Thus, it should be our topmost priority to treat and cure this disease.

Question: 40 million people in India are HBV infected and constitute about 11% of the global rate. What would you say Dr. Arora?

Dr. Arora: This topic is very pertinent as Covid will come and go but the illnesses like Hepatitis have not gone ever since. Certain viruses are spread through contaminated water and infected fluid, which are totally preventable. This is a prevalent issue in developing countries like India and South Asian nations whereas it has been totally eradicated in developed countries. Simple provision of safe drinking water and hygiene can prevent Hepatitis A & E. Virus spread through parental route are problematic. Hepatitis B & C are neglected, and like you said there are 40 million carriers of the infection unaware of the fact that they are infected, hence they are not only potentially disease developers but are also becoming a threat for their families. By increasing awareness, we can prevent this.

Question: Dr. Khanna would you agree with Dr. Arora that there is a problem of awareness that needs to be tackled right away?

Dr. Sudeep Khanna: I would like to add something to it, people know that something like this exists but they are not ready to accept it. A recent study conducted on 1 lakh children from India concluded that only 50% of the children were vaccinated against Hepatitis B.

Question: Isn’t it covered under Universal Health Immunization? Then why aren’t people getting vaccinated?

Dr. Sudeep Khanna: For the same reason as why they wouldn’t get anti-covid vaccine. This becomes a problem for us to help people. The vertical and horizontal transmission from mother to baby and during close contact is the most common cause of Hepatitis B. People need to be tested, treated and educated.

Question: Dr. Arora, we rightly spoke about how people are not even ready to accept it. So what can people do to prevent this stigma?

Dr. Anil Arora: A wonder drug called DAA has been discovered which can cure almost any type of Hepatitis C and hence it is as curable as any other disease but Hepatitis B is problematic. They are not aware of the fact that they may be carrying the virus in their blood for ages before they come down with advanced diseases like Cirrhosis and Carcinoma. My advise will be that anybody with a history of liver transplant, blood transmission, surgery, needle prick trauma or even dental manipulation should get a checkup for Hepatitis B. Now coming to vaccination, Hepatitis B vaccines has been available for over three decade at very low rate and very efficient.

Question: There are about 1.1 million who have died due to Hepatitis, and 3 million are still carrying the disease worldwide. How do we really address this in India especially with the urban rural divide?

Dr. Sudeep Khanna: Multimedia and TV are such a big medium and still unused to their full capacity. A lot of people don’t know about Hepatitis C and lack of initiative from the authorities and doctor bodies are causing this. The disease is significantly asymptomatic and by the time they are symptomatic it is too late. So it is all about awareness.

Question: Dr. Arora, what can one do if one is already infected with Hepatitis B? What about cure?

Dr. Anil Arora: There are two aspects of patient suffering from Hepatitis B, unlike other illnesses, if someone gets an infection today, there are 5% chances that as an adult they will carry the virus in the blood for the next 6 months that is called chronic carrier state and may develop the disease later in life. They remain asymptomatic and thus do not bother about it. This is where screening is needed and if a person is accidentally positive for Hepatitis B, he can be treated with antiviral therapy or else he may spread it to his family. In early diagnosis, regular follow up goes a long way in preventing the chronic illness.

Question: Dr. Saigal, can a patient of Hepatitis B follow up with their checkup if infected with Covid?

Dr. Sanjiv Saigal: Patients ask that if I am Covid positive then what happens with the other problems of mine and if you look at Hepatitis, the patients are consulting specialist doctors, and hence can manage with a teleconsultation and it is not required to come to the hospital. If there is an emergency, then they should visit the hospital no doubt. If a Hepatitis patient is Covid positive and taking the concerned medications, I would recommend that they don’t stop taking medicines for Hepatitis as this may provide a flare to the disease.

Question: Dr. Khanna, are the patients with Hepatitis at a greater risk if they get Covid? Are they furthermore immunosuppressed like we have seen in Cirrhosis?

Dr. Sudeep Khanna: If one has Cirrhosis, they are not at higher risk of getting infected. If in case the liver function goes down, the risk of Covid complication increases. Similarly, being infected with Hepatitis B or C does not mean that you are at higher risk of getting Covid. There should be no fear of vaccination.

Question: Dr. Arora, what would you say on the point “ No fear of vaccination”?

Dr. Anil Arora: Liver is a vital organ in many functions including metabolism and immunity. Once you have severe Covid, liver gets involved in the immunity in many patients. Patients who have underlying liver disease should be given vaccine on a priority basis. Because liver handles all the drugs given to the covid patient.

Question: In what conditions in Covid patients does it lead to diseases like Cirrhosis other complications?

Dr. Sanjiv Saigal: If you develop Jaundice due to contaminated food or water, it is a small chance that they may develop rapid deterioration and altered sensorium thus may have to be admitted to ICU. If someone has chronic disease like Hepatitis B or C and catch infection like Pneumonia, Covid, etc. then they may develop a liver failure. These are the two situation which may cause rapid deterioration and both the type of patients should be diagnosed early and quick treatment can save these patients.

Question: How can the person know that they are carrying the Hepatitis infection?

Dr. Sudeep Khanna: For most of the patients, the disease is asymptomatic. And hence is it not possible for them to diagnose through symptoms. Tiredness, although is a primary symptom so if you have fatigue throughout the day, you may have Hepatitis. One other way is to know if a family member is diagnosed with Hepatitis, one may be a carrier for the disease. Also, screening the high risk population is a way out.

Question: Dr. Arora, we spoke about who all should get tested, what will be your suggestion to all the policy makers?

Dr. Anil Arora: the only way to pick it up early and diagnose is by testing. So my suggestion is that whenever going for any sort of blood test or screening, get tested for Hepatitis B and C. and executive check up is becoming a routine. It should be mandatory and if an asymptomatic patient is not checked up early, the cost of long-term disease treatment is enormous. While it is very cost effective in early stages.

Question: Dr. Saigal, is there anything that we can do to prevent it other than screening or vaccination?

Dr. Sanjiv Saigal: As we discussed, we have to identify the high risk population. We need to look for any family member with Hepatitis. If you have a liver problem, you should get it checked. Then you need to avoid contaminated food and liquid. Be careful in interpersonal relationships. Dialysis and following all protocols strictly may help diagnose and treat Hepatitis. We should follow universal practice of screening people. Be aware and screen people which may help people to curb the disease.

Question: what do you suggest policy makers, institutions and common people to eliminate the disease?

Dr. Sudeep Khanna: As an individual I can only think of vaccine being made mandatory which is very difficult in the democracy. Other than that nothing is going to help.

Since we all go to annual checkups, our panelists suggest that do get checked up for Hepatitis on a routine basis, avoid contaminated food and get proper vaccination.

Sudden Cardiac Arrest is the most leading cause of preventable deaths in India. It can occur to any person rich or poor, anywhere, even without any pre-existing cardiac diseases. Many important dignitaries of the Nation have succumbed sudden Cardiac Arrest. The incidence is more than covid-19.

Less than 2% of the population in India are aware of CPR. Most of the victims unattended or treated by local methods of superstitions. About 4280 people per one lakh population are prone to Sudden Cardiac Arrest every year and nearly 90% succumbed to death.  The Sudden Cardiac Arrest the cause for 59,064,000 preventable deaths in a year in India. And 161,819 per day, ie 6742people get Sudden Cardiac Arrest in an hour. India is a poor country with very meager per capita income and can’t afford an expensive training.

1.38 billion population in India. A sort of Indian guidelines and trainings is a must. Indian Resuscitation Guidelines will give confidence in all medical fraternity and among people, will save life’s, bring unity among organization. They need training in the local languages.

Indian Society of Anaesthesiologists has convened a meeting on 16^th April 2017 at Hyderabad inviting many people involved in CPR in India. Indian Society of Anaesthesiologists, Indian society to study pain, Research society of Anaesthesiology and clinical pharmacology, Indian association of Cardiothoracic Anaesthesiologists, Indian Medical Association, Dr. NTR University of Heath Sciences, Indian Society of Critical Care Medicine, Association of Obstetric Anesthesia, UP Rural Institute of Medical University, Indian Association of Pediatric anesthesia , GVK EMRI, 108, Indian society of perinatology and reproductive biology, Indian College of Anaesthesiologists, and some members of Emergency medicine from different cities. It is resolved that India should have its own guidelines of resuscitation, as we do not have proper emergency medical system, equipped Ambulances, AEDs. We have different cultures, languages, customs, religions, inaccessible areas and superstitions. We studied the available literature available on similar circumstances around the world, less effluent countries and brought out the guidelines, and published in a PubMed Indexed journal after peer reviewing. Thus, a MAKE IN INDIA guidelines prepared to serve Indians.

• Ahmed SM, Garg R, Divatia JV, Rao SC, Mishra BB, Kalandoor M V, Kapoor MC, Singh B. Compression-only life support (COLS) for cardiopulmonary resuscitation by layperson outside the hospital. Indian J Anaesth [serial online] 2017 [cited 2021 Jul 12];61:867-73. Available from: https://www.ijaweb.org/text.asp?2017/61/11/867/218099
• Garg R, Ahmed SM, Kapoor MC, Mishra BB, Rao SC, Kalandoor M V, Divatia JV, Singh B. Basic cardiopulmonary life support (BCLS) for cardiopulmonary resuscitation by trained paramedics and medics outside the hospital. Indian J Anaesth [serial online] 2017 [cited 2021 Jul 12];61:874-82. Available from: https://www.ijaweb.org/text.asp?2017/61/11/874/218100

• Garg R, Ahmed SM, Kapoor MC, Rao SC, Mishra BB, Kalandoor M V, Singh B, Divatia JV. Comprehensive cardiopulmonary life support (CCLS) for cardiopulmonary resuscitation by trained paramedics and medics inside the hospital. Indian J Anaesth [serial online] 2017 [cited 2021 Jul 12];61:883-94. Available from: https://www.ijaweb.org/text.asp?2017/61/11/883/218102
• Singh B, Garg R, Chakra Rao S S, Ahmed SM, Divatia J V, Ramakrishnan T V, Mehdiratta L, Joshi M, Malhotra N, Bajwa SJ. Indian resuscitation council (IRC) suggested guidelines for comprehensive cardiopulmonary life support (CCLS) for suspected or confirmed coronavirus disease (COVID-19) patient. Indian J Anaesth [serial online] 2020 [cited 2021 Jul 12];64, Suppl S2:91-6. Available from: https://www.ijaweb.org/text.asp?2020/64/14/91/284914

The motto of Indian Resuscitation council is to make Every Citizen a Lifesaver

Train your neighbors and save yourself

Your two hands can save lives

We postulated the technic of Compression only Life Support (COLS) where a layperson can perform Cardiopulmonary resuscitation with his two hands outside the hospital and even useful for the Army personal.

We have many challenges ahead, to make Every Citizen A LifeSaver

13 million school children every year need to training Basic cardiopulmonary life support (BCLS)

83,000 medical students need mandatory certificate in Basic Cardiopulmonary life support and Comprehensive cardiac life support (CCLS)

200,000 nurses need of certify every year in BCLS and CCLS across nation

Only 1 % out of cardiac arrest attempt was done in India vs 40% in western countries.

We Indian Resuscitation Council established in 2017 participated in WRAH Day and trained school children and laymen.

Over 675,000 lay people trained in

cardiopulmonary resuscitation

worldwide — The “World Restart a Heart

(WRAH)” initiative 2018

Available online at www.sciencedirect.com

Resuscitation journal homepage: www.elsevier.com/locate/resuscitation

The Indian Resuscitation Council, members of the Indian Society of Anaesthesiologists, and other professional, societies performed nationwide CPR training of laypeople in high schools, colleges, bus stations, railway stations, police stations, company offices, and other public places. At least 30 federal states of India participated and many

Chief Ministers and Health Ministers were actively involved. Overall, 225,000 people were trained in India for WRAH 2018.

Up to 206 million People Reached and Over 5.4 million Trained in Cardiopulmonary Resuscitation Worldwide: The 2019 International Liaison Committee on Resuscitation World Restart a Heart Initiative

INDIA IRC/ ISA : No trained in COLS are 500,268 , in 2019,

Vice President of India Sri Venkaiah Naidu released in BCLS manual in November 2018.

Vice President of India Sri Venkaiah Naidu released the CCLS manual in July 2019.

2020 March Covid19 has slowed down our progress.

Since 2018, IRC is attending all the bimonthly meetings of WRAH Day. Demonstrated CPR in Heritage sites, prepared songs, skits on CPR, in different languages including Urdu and Kashmiri.

Released 1^st day envelop and stamp on the occasion of WEAH Day on 16^th October 2020, by the Andhra Pradesh State Minister, Member of the Parliament and the Member of Legislative Assembly, in the virtual presence of WRAH Day, AAPI and ISA dignitaries.

COLS basic CPR guidelines are included in 12^th grade nationwide school’s syllabus in July 2021

-Mandatory Certification of Basic cardiopulmonary life support before graduation in state of Andhra Pradesh by Dr NTR University of Health Sciences, Andhra Pradesh of 50 million population,6000 medical student graduated,

National Medical commission has introduced a foundation course for the newly admitted students of MBBS and they have incorporated BCLS for them

Establishing IRC Resuscitation Training centers in medical colleges across country

Training of trainers (TOT) across country is going on every two months. A separate dedicated training started for all the hospital staff with National Accreditation Board for Hospitals and Health care providers (NABH) (like joint council of hospitals). NABH certifying body of 30,000 private and thousands of govt hospital, who has mandatory certification for BCLS to all Doctors, nurse and paramedics working from front office to the high dependency areas

Providing affordable courses through IRC part of ILCOR will have more support and on an international platform as health is global.

We must have heard or seen situations like “A 50-year-old man jogging in the park. He suddenly collapses and people in the park surround him” Or “Oh ! he was well last night, I have talked to him, but expired suddenly in the early morning” And we keep wondering what could be the reason!!

Every year, about 4,280 out of one lakh victims of sudden cardiac arrest (SCA) die in India. Sudden cardiac arrest is a condition where the heart stops its function of pumping blood to the whole body leading to the cessation of heartbeat and breathing. The terms cardiac arrest and heart attack are often used interchangeably, but these are two different conditions. A heart attack occurs when an artery is blocked due to fat and cholesterol deposition and prevents blood from reaching the heart muscle causing severe chest pain and breathing difficulty. Whereas cardiac arrest often occurs suddenly without any warning due to disturbance in the electrical activity of the heart that causes an irregular heartbeat (arrhythmia) which disrupts the heart’s ability to pump blood to the brain, lungs, and other vital organs. Disturbance in the electrical activity of the heart leading to cardiac arrest can be due to any of the following reasons: diabetes, hypertension, lungs, liver and kidneys diseases, etc. However, it can happen to anybody at any point in time. Within few minutes of cardiac arrest, the victim becomes unconscious and death occurs within minutes if the victim didn’t receive treatment. It has been observed that “ Every minute’s delay in the resuscitation of the cardiac arrest victim reduces the chance of survival by 7-10%”. So a prompt action can save the person’s life with cardiac arrest.

India is a vast country with lots of diversity, differences in culture, language, religions, customs, atmosphere, socio-economic issues, and differences in terrain. The environment and the infrastructure for resuscitation of a person with sudden cardiac arrest vary from place to place. So there was a need for a structured guideline to be followed for resuscitation of cardiac arrested victims. Moreover, the approach should be such that it is applicable at all scenarios and remains scientifically valid. There is a large body of evidence to show that it is possible to save the victims of SCA with immediate high-quality bystander hands-only cardiopulmonary resuscitation (CPR) – Compression only life support (COLS)

Compression only life support (COLS) are the guidelines developed by the Indian Resuscitation Council for providing only chest compressions in a stepwise algorithmic approach by a layperson for the cardiac arrest victims till the time medical help arrives

The timely management of the victim with cardiopulmonary arrest is paramount. It may not be possible to provide immediate medical care by the trained person when the victim is outside the hospital. The inclusion of common man after their proper training would be beneficial to improve the outcome of the victim. However, the medical steps to be taught to a layperson should be kept simple and easy to follow, and yet evidence-based.

Learning the skill of saving one’s life is may not be easy. But it is equally not easy to ignore someone dying unattended. Let us all try and make a world where no one dies from cardiac arrest. The Compression only Life Support (COLS) provides an easy, algorithmic stepwise approach for resuscitation of the victim with cardiopulmonary arrest by the lay person. To save one’s life, you should know various steps of COLS-Compression Only Life Support.

1. Ensure Scene safety
2. Victim’s response check
3. Call for help and emergency medical system
4. Early and effective chest compression
5. Transfer to the health facility

The main activity of Compression-Only Life Support (COLS) is effective chest compression which should be performed continuously till help arrives. The chest compressions are performed at the rate of 120 per minute and the depth of each chest compressions should be around 5-6 cms.

To enhance the outcomes in cardiac arrests we need high-quality adult resuscitation education and Hands-on Training to maximum citizens. To achieve this, we first need to create the awareness and creating confidence among laypersons, that their contribution is equally important for the survival of a sudden cardiac arrested victim outside the hospital.

The main motto of any project related to layperson training in CPR is to bring out wide popularity for resuscitation, impart training to as many laymen including school children so that every citizen becomes a lifesaver. The IRC aims to train at least one person in the family to save the life from sudden cardiac arrest.

So, remember, Each of one us can save a life. Your two hands can save a life. Your timely help with compression-only CPR (COLS), in this emergency, may save somebody’s life. This victim could be your family member, friend, or a stranger on the street! Let us take a pledge on this National CPR day to learn CPR.

About the authors: 

• Mr Aditya Kumar is an Honorary Director Public Relations at Indian Resuscitation Council.
• Dr Rakesh Garg  is an Honorary Scientific Director at Indian Resuscitation Council.

Aunty 1: The baby looks so thin, Baby needs cow’s milk, my dear. Me: Cow’s milk is for cow’s baby, my baby needs my milk.

Aunty 2: Oh God, such small breasts you have, how will your milk be enough? Me: My body has the capacity to create however much milk needed for my baby and you know it is the best food for her

Aunty 3: Don’t feed your baby so long, you are pampering him, he will never leave you. Me: How can you pamper your baby by nourishing him?

Aunty 4: Look at you, with the baby all the time, in our times we used to do all the household work and brought up so many kids as well. Me: bringing up a baby with love, care, and breastmilk is our choice as parents and we need all your help and support to successfully do it

Let’s ponder, how many of us have been the Aunty or ME in the above conversations in our lives? Almost all, right? Being a first-time mother at the age of 33 was not easy for me, to have a baby late was not a choice as well. Being a pediatrician was a privilege and personal life took a backseat in the pursuit of higher studies. I thought I knew the solutions to all the challenges of breastfeeding, but reality was far from different. As the saying goes “It takes a village to bring up a baby”, in the modern times “it takes an entire family to breastfeed a baby”. Urbanization, nuclear families and career goals have made the art of breastfeeding less familiar to many of the millennial to-be mothers. We want the best for our baby and we know that breastfeeding is the best path. However, many of us land up being a bundle of nerves when our babies arrive, not sure where to start and how to go about. Agreed that breastfeeding is natural both for mother and the baby, but we forget to warn the to-be mothers that it is a helluva painful, stressful and exhilarating ride. To top it all, mothers also have to deal with the benevolent, free-advice churning Aunties and Uncles in the midst of this roller-coaster. Many a time, the well-wisher could be our own father, mother or even husband. Equipped with knowledge and confidence, I could defend and retort to many of them. However, the dream is to equip every mother of our land with enough knowledge to be the ME in the above situations.

Adequate breastfeeding is a single practice that can prevent lakhs of children from dying, worldwide. World health organization and UNICEF recommends that breastfeeding is initiated within 1^st hour of birth, baby be given nothing but mother’s milk till 6 months and breastfeeding to be continued till 2 years of age and beyond. The global rates for breastfeeding are 43%, 41%, and 45% at 1^st hour, 6 months, and 2 years, respectively. So, it is not as universal as it has to be. Survey by POSHAN reported that in India, exclusive breastfeeding rate is 54.9%. Mothers face many a challenge like feeling of inadequate milk, household chores, expectations from workplace, pressure to supplement with formula etc. She needs the support of her near and dear ones as well as the community to overcome these hurdles. Currently, mothers can get guidance from ASHA/ anganawadi worker, and gain knowledge through materials circulated by Government of India via Radio and TV. She can also access various peer groups in social media as well as consult trained lactation counsellors. World Breastfeeding week celebration is celebrated every year in the 1^st week of August and this year the theme is “Protect breastfeeding- a shared responsibility”. Breastfeeding no longer can be left as “ladies’ matter”. Confident, and knowledgeable mothers are the foundation of future generation. Hence, lets come together to support our mothers and become the true “well-wishing” Aunties and Uncles for our younger ones.

The findings of a new study suggest that remotely supervised workout sessions are more effective than face-to-face exercise classes during the COVID-19 pandemic. The findings of the study appeared in the journal ‘Psychiatry Research’. Researchers at the University of Sao Paulo (USP) in Brazil investigated the effects of regular exercise on the physical and mental health of 344 volunteers during the pandemic.

The study compared the effectiveness of three techniques: sessions led in person by a fitness instructor, sessions featuring an online instructor but no supervision, and sessions supervised remotely by an instructor via video call. The two kinds of sessions with professional supervision had the strongest effects on physical and mental health. According to the researchers, this was due to the possibility of increasing the intensity of the exercises over time.

To their surprise, remotely supervised sessions were more effective than face-to-face sessions. Sedentary subjects served as controls. “The findings underscore the benefits of either approach, with the instructor online or physically present, compared with being sedentary. However, the physical and mental benefits have much to do with a secure and progressive increase in the intensity of the exercises, which occurred only when they were supervised by a professional. What’s interesting is that remote supervision by video call was more efficient. The difference was small but statistically significant,” Carla da Silva Batista, last author of the study, told Agencia FAPESP.

Batista is a researcher at the University of Sao Paulo’s School of Physical Education and Sports (EEFE-USP). The study was supported by FAPESP. Volunteers were selected from different age and income groups and came from different parts of Brazil. Some had symptoms of depression. The remotely supervised participants, who worked out using Pilates, Crossfit, yoga, dance and aerobics, exercised more intensely than those who lacked supervision.

“Increasing intensity in supervised online sessions was of paramount importance during the pandemic,” Batista said. “Around half the participants, or 55 per cent, performed high-intensity exercises before the pandemic, but the proportion fell to 30 per cent once lockdown began.” Other research shows intense exercise increases longevity, reduces the risk of developing Parkinson’s disease, and is associated with a reduced risk of 26 types of cancer.

“We don’t know exactly why working out with remote supervision by video call gets better results than when the instructor is physically present,” Batista said. “It’s probably that the participants felt the discomfort of wearing a mask hindered their performance during the pandemic.”

Other reasons could include the possibility that remotely supervised participants were more motivated. “They were doing exercises in safety and at home, but with supervision and without having to wear a mask. They didn’t have to worry about spreading the virus, so the instructor may have felt free to increase the intensity of the exercises safely, without risking injury or discomfort,” Batista said.To evaluate the participants’ physical and mental health, in July-August 2020 the researchers applied validated online questionnaires known as the International Physical Activity Questionnaire – Short Form (IPAQ-SF) and the Montgomery-Asberg Depression Rating Scale – Self-Rated (MADRS-S).

A new study has found that a group of chemotherapy drugs can result in mutations that may trigger the relapse of blood cancer in children.Chemotherapy has helped make acute lymphoblastic leukemia (ALL) one of the most survivable childhood cancers. Now, researchers working in the US, Germany and China have shown how chemotherapy drugs called thiopurines can lead to mutations that set patients up for relapse. The findings of the study were published in the journal ‘Nature Cancer’.

The research provided the first direct genomic and experimental evidence in pediatric cancer that drug-resistant mutations can be induced by chemotherapy and are not always present at diagnosis. “The findings offer a paradigm shift in understanding how drug resistance develops,” said Jinghui Zhang, PhD, Department of Computational Biology chair at St. Jude Children’s Research Hospital.

“The results also suggest possible treatment strategies for ALL patients who relapse, including screening to identify those who should avoid additional thiopurine treatment,” added Zhang. Zhang is co-corresponding author of the study with Bin-Bing Zhou, Ph.D., of Shanghai Children’s Medical Center; and Renate Kirschner-Schwabe, M.D., of Charite-Universitaetsmedizin Berlin.

THE ROOTS OF RELAPSE

While 94 per cent of St. Jude patients with ALL become five-year survivors, relapse remains the leading cause of death worldwide for children and adolescents with ALL. This study involved ALL samples collected from relapsed pediatric ALL patients in the US, China and Germany. Researchers analysed more than 1,000 samples collected from the patients at different times in treatment, including samples from 181 patients collected at diagnosis, remission and relapse.Co-first author Samuel Brady, PhD, of St. Jude Computational Biology, identified a mutational signature that helped decipher the process. Mutational signatures reflect the history of genetic changes in cells.

Brady and his colleagues linked increased thiopurine-induced mutations to genes such as MSH2 that become mutated in leukemia. The mutations inactivated a DNA repair process called mismatch repair and rendered ALL resistant to thiopurines. The combination fueled a 10-fold increase in ALL mutations, including an alteration in the tumour suppressor gene TP53. The mutation, TP53 R248Q, promoted resistance to multiple chemotherapy drugs, including vincristine, daunorubicin and cytarabine.