How did this journey start?

The journey began in 2021 with a 29-year-old woman who was daring enough to choose this option. At that time, I was not entirely sure which patients should be given the option for stem cell transplant or whether we should continue with rituximab, tocilizumab, mycophenolate, and other modalities that constitute our standard care treatment. Having attended multiple lectures by Dr. Dinesh Khanna during his visit to India, where he strongly emphasised the advantages of stem cell transplantation in scleroderma, it has always been on my mind. However, it was crucial to select the right patient, considering the risks and mortality associated with it.

This patient was diagnosed with Systemic Sclerosis (Scl-70 positive) 2 years ago in 2019. Initially, she had more skin involvement than lung involvement, but after marriage, she defaulted on treatment, and the disease returned significantly, worsening her ILD. Despite trying Mycophenolate/Azathioprine, her symptoms continued to deteriorate. I switched her to Cyclophosphamide, but she couldn’t tolerate the intravenous dosing, and it had to be discontinued after the third dose. When offered Rituximab, she refused and wanted a permanent solution. As we know, it still doesn’t get cured, but we proceeded with the patient’s choice and planned our first procedure across Pan-Fortis.

What were the challenges you came across?

When you choose to introduce new treatments in your practice, two main challenges arise: from the doctor’s perspective, is it an approved treatment (for medical ethics)? How effective is the treatment we are offering? What are the possible complications of the procedure, and what are the outcomes? From the patient’s perspective, it involves all these factors, including the cost of the treatment, as it is being done in a private setting without any insurance willing to cover the disease. For all medico-legal purposes, we ensured that we obtained the consent of the patient and their family, recorded under video. As the procedure cost was around 15 lacs, we held a strong fundraiser for the patient and managed to raise about 6-7 lacs. 

And then the final time came through. For a patient who couldn’t initially tolerate Cyclophosphamide, we had planned a much heavier regimen this time. For the first time, we used a combination of Rituximab, ATG, and Cyclophosphamide, which had not been used in other HSCT trials before. Pre-screening was done with DTPA, Stress Echo, CMV, JC Virus, and other viral markers. CD34+ cells were isolated before the procedure. The patient underwent the regimen over 4 days, followed by a Stem Cell Transfusion. A lot of side effects, including nausea and hair shedding, began, but somehow the patient tolerated it. As for the first patient, she developed a fever and shortness of breath on Day 12 of the procedure and had to be shifted to the ICU for the first day. After increasing antibiotics with no cause for infection found, it was diagnosed as Engraftment syndrome, and we increased her steroids. The patient required several blood products over the next 7 days but was discharged in a stable condition.

How has the journey been so far?

“A great discovery is a fact whose appearance in science gives rise to shining ideas, whose light dispels many obscurities and shows us new paths.” By Claude Bernard

For us, it was the index case. We followed her for a year, and to our surprise, her skin cleared up and the ground glassing in the lungs resolved. She returned to her everyday life and has been without treatment for four years and counting. Her improvement gave us hope of offering better treatment to systemic sclerosis patients and may provide a window for a drug-free life. A year later, we had the second patient who was in the worst condition of all 15 patients treated. Coming from Nellore and having been under the care of a fine rheumatologist, she had failed multiple therapies (IVIG, Rituximab, Cyclophosphamide). As she was completely wheelchair-bound, it was going to be a challenge. But post-treatment, she has become a different person. Without any ongoing treatment for three years post-transplant, she now takes yoga and dance classes for systemic sclerosis patients.

We have performed HSCT for 15 patients, with the youngest being 11 years old and the oldest 40 years old. The average disease duration has been 2.5 to 3 years, with only one patient, aged 11, still experiencing active disease. Thirteen patients had lung involvement, while 2 had only skin involvement. There were no mortalities during the procedure. Four patients had an ICU stay from day 8 to day 10 for 1-2 days, but recovered fully. Currently, 12 patients are completely off treatment, showing remarkable improvements in skin scoring (Rodnan Score: 3/3 to 1/3) and no progression in ILD. More importantly, they have discontinued medications. For 2 to 3 patients with some fibrosis, Nintedanib has been continued. Only one patient developed myocarditis following the transplant, and another experienced worsening Raynaud’s (both male patients). The female patients had better clinical outcomes. For the patients, we learned that cardiac monitoring and ruling out PAH are paramount, especially when high-dose cyclophosphamide is to be administered. Hence, we also included Cardiac MRI in our protocol.

Please let us know about your team.

Our haematology team is led by Dr. Rahul Bhargava, who has performed over 500 transplants across various conditions to date. Therefore, we ensured that our clinical rounds included an intensive care doctor, a rheumatologist, and a haematologist, as well as alternate-day screenings by a cardiologist for echocardiograms, and daily visits from a dietitian. Through our combined efforts, we have achieved positive clinical outcomes for our patients.

What is your roadmap for the future?

I want to focus on creating more awareness about the benefits of stem cell transplants. With CAR T-cell Therapy emerging, both options will benefit patients with Systemic Sclerosis. Not only does it halt the disease, but it also offers them a life free of medicines. However, we definitely need to reduce the cost of treatment so more people can access it. Including it in insurance may help patients obtain this life-saving procedure. However, we are still learning; considering it is a new procedure, over time we will gain a better understanding of whether the disease flares up again or not.