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| EDITORIAL |
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| Year : 2019 | Volume
: 65
| Issue : 1 | Page : 1-4 |
Access to hematopoietic stem-cell transplantation in India
U Kulkarni, B George
Department of Haematology, Christian Medical College, Vellore, Tamil Nadu, India
| Date of Web Publication | 28-Jan-2019 |
Correspondence Address:
Dr. B George
Department of Haematology, Christian Medical College, Vellore, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jpgm.JPGM_391_18
How to cite this article:
Kulkarni U, George B. Access to hematopoietic stem-cell transplantation in India. J Postgrad Med 2019;65:1-4 |
Hematopoietic stem-cell transplantation (HSCT) is a curative modality for a number of benign and malignant disorders;[1] however, there is a significant cost associated with this process. In India, there is still a vast difference between the patient needs and the health-care delivery.[2] A recent household survey in India has estimated that approximately 38 million people have been pushed below the poverty line due to spending on medicines on a number of diseases including cardiovascular disease and cancer.[3] It is in this context that we need to examine the use of HSCT as an appropriate tool to cure Indian patients suffering from hematological disorders.
India has a large population of 1.34 billion as per estimates in 2018 and one would expect a proportionate large number of patients diagnosed to have acute leukemia, a proportion of which will require HSCT. In addition, a few diseases are much more common in Asian countries, including thalassemia major and aplastic anemia, for which HSCT is the treatment of choice. There is, however, a wide gap between establishing a diagnosis and obtaining standardized treatment. For example, at our center, almost 71% patients with acute myeloid leukemia were recently unable to undergo treatment with the standard of care, mostly due to financial constraints.[4] The proportion of patients not pursuing treatment may be lesser at centers where the treatment costs are subsidized through funding from the government and charitable trusts. However, as compared to the projected need considering the disease prevalence, the proportion of patients having treatment at such centers is not very large.[5] This is true not just for chemotherapy alone but also for HSCT with a significant gap in the projected need calculated as per disease prevalence and the actual number of HSCTs performed in India.[6] It is estimated that about 12,000 new thalassemics are born annually in India, of which 30% (3600) might have suitable donors available for HSCT.[7] However, the total number of HSCT done for thalassemia between the years 2012 and 2016 at centers reporting to the Indian Stem Cell Transplant Registry (ISCTR) is only about 960 (personal communication with ISCTR). Data from two large Indian centers suggest that among patients diagnosed to have aplastic anemia, only 20–30% receive what is considered standard of care, that is, HSCT/immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporine.[8],[9] Thus, there is a large need for improving access to HSCT in India. Recently, a large international registry-based study suggested that early post-HSCT survival in acute lymphoblastic leukemia was linked to country-level macroeconomic indicators.[10] Although the reasons for this association are unclear, it was possibly linked to factors like variations in supportive care, level of training of the staff and intensive care facilities. Thus, developing countries like India have challenges beyond just improving access to HSCT.
Addressing this problem needs a multipronged approach, which includes increasing the number of transplant centers, improving minimum standards for HSCT centers, reducing overall costs associated with HSCT, and helping patients with financial support for HSCT.
| :: Transplant Centers | |  |
There are different types of hospitals offering HSCT in India, namely, public hospitals, corporate hospitals, not-for-profit trust hospitals, and hospitals for the armed forces. Many of these are members of the ISCTR, which is a not-for-profit organization established in 2004 to share clinical experience, promote cooperative studies, and maintain data by coordinating between different centers. There has been a steady rise in the number of HSCT centers and also the number of HSCT done per year in India, which is an encouraging sign for the country. At present, there are 65 transplant centers reporting their data to the ISCTR,[11] but it is still inadequate considering the large population in India. Although it is important to develop more centers, it is also important that all centers, both new and old, maintain minimum standards in order to ensure that appropriate health care is delivered to all patients. For developing countries, the Worldwide Networks for Blood and Marrow Transplantation has laid down requirements for establishing a HSCT unit in three levels of care (minimum, preferred, and ideal).[12] The minimum standards for HSCT units in India have also been laid down.[13] Data on the exact need for HSCT in terms of prevalence of various indications for HSCT, the start-up and sustainability costs of an HSCT center along with the costs of quality assessment and improvement programs, availability of trained transplant physicians and nurses, laboratory services including Human Leukocyte Antigen (HLA) and blood banking, and requirements for accreditation need to be addressed while starting an HSCT center.[12] Toward improving access to HSCT in India, training of physicians and nurses are a prerequisite. At present, formal training in HSCT is being offered at a few HSCT centers in India (nine centers conducting the DM course in hematology and five centers conducting the DNB course in hematology), and therefore, it is important that more centers take up appropriate training of physicians and nurses in the field of transplantation. Physician training is also available via fellowship courses in stem-cell transplantation at a few centers. Training of apheresis technicians, transplant nurses, coordinators, and data management teams is also equally important. Groups like the ISCTR can give a platform to organize such training opportunities via interactions between various HSCT centers. Besides the availability of HSCT centers with expertise and the costs, the other challenge toward making HSCT more accessible is the availability of donors for HSCT. Since only 30% of patients will have a HLA-matched sibling or family donor, it is important that large donor registries are available in India, which will give patients access to a large number of voluntary donors. HSCT using HLA haploidentical family donors or HLA-matched unrelated donors from stem-cell donor registries are being increasingly performed at various centers in India. In fact, between 2012 and 2016, data submitted to the ISCTR suggest that for patients above 18 years, the donor source was matched unrelated in 7% and haploidentical in 15% (personal communication with ISCTR).
| :: Disease Prevalence and Cost Data | | |
Data on disease prevalence for disorders where HSCT can offer a cure are being increasingly generated in India.[5],[7],[14],[15] Data on estimated costs of hospitalization for HSCT are also available.[16] The direct in-hospital cost (from initial hospital admission till discharge) of an autologous HSCT is approximately INR 4–7 lakhs, whereas that of a matched related HSCT is approximately INR 11–17 lakhs. For unrelated donor HSCT, the cost is approximately INR 21–28 lakhs (excluding the cost of the graft), whereas for haploidentical HSCT, the cost is approximately INR 21–28 lakhs. Depending on the type of the donor and the complications, the cost of HSCT varies between INR 14 and 52 lakhs. Of these, 50–60% represents drug costs, 15–20% is bed and nursing charges, 10–15% is investigation charges, and 5% is blood product charges, whereas 10% is professional fees. In addition to these costs, there are other direct costs such as posttransplant admission, outpatient costs, cost of accommodation, travel, and food peritransplant and indirect costs such as lost wages for the patient and family members.[17],[18],[19] However, the per capita gross domestic product for India is only about INR 1.2 lakhs. These differences necessitate cost-effectiveness analyses to guide policy makers to allocate resources for HSCT in India. Data from India on such analysis for a few disorders[20],[21] are also available.
Cost seems to be a major barrier toward making HSCT more accessible in India. Most of the payment for HSCT is out of pocket.[2],[17] Other prevalent sources for payment are health cover via the employers or government health schemes, personal health insurance, corporate social responsibility schemes, charitable donations from nongovernmental organizations, or crowd funding. Health cover via employers is available to few. Health cover via government schemes will make a broader impact. For example, the Tamil Nadu Chief Minister's Comprehensive Health Insurance Scheme is very useful as it provides almost complete financial assistance for HSCT.[22] Moreover, central government and armed forces' institutions have near complete financial assistance available. Additionally, the ministry of health of the central government and one of the public sector undertakings, the Coal India Limited (CIL), are providing funding for HSCT for thalassemia under a CIL corporate social responsibility program.[23] Partial financial assistance is available from Prime Minister's National Relief Fund and charitable trusts like Tata Trusts.
In order to understand the extent of out-of-pocket payment for autologous and matched related donor HSCT at our center, which is a not-for-profit trust hospital, we conducted a retrospective analysis of the total direct admission costs of HSCT at our center over the last 1 year for patients undergoing HSCT. We recorded the financial assistance including Prime Minister's National Relief Fund, funding from Tata Trusts, Chief Minister's Health Insurance Scheme, CIL corporate social responsibility program, personal insurance, and employer health cover that was availed for patients undergoing HSCT. At our center, during the year 2017, a total of 235 HSCTs were performed. Of these, 75 were autologous HSCTs, whereas 160 were allogeneic HSCTs, of which 86 were matched related donor HSCTs. [Table 1] and [Table 2] show the indications for autologous and allogeneic HSCT performed in the year 2017 at our center. For autologous HSCT, the median total direct admission cost was INR 583,960 (range INR 284,255–2,041,345). Of the 75 patients who underwent autologous HSCT, 27 patients (36%) received financial assistance of a median of 73.11% of the total direct admission costs (range 11.68–102.75%). Of the total direct admission costs for 75 patients who underwent autologous HSCT, the total financial assistance availed was for 25.32% of the costs, whereas the remaining 74.68% payment was out of pocket. For matched related donor HSCT, the median total direct admission cost was INR 1,141,234.5 (range INR 689,560–3,585,235). Of 86 patients who underwent matched donor HSCT, 46 patients (53.49%) received financial assistance of a median of 66.94% of the total direct admission costs (range 3.25–100%). Of the total direct admission costs for 86 patients who underwent matched donor HSCT, financial assistance availed was for 32.78% of the costs, whereas the remaining 67.22% payment was out of pocket [Table 3]. Thus, there is still a large need to improve the financial support available for HSCT. In addition, the limitation of the above analysis is that we have considered only the total direct admission cost of HSCT. Other direct costs such as posttransplant admission, outpatient costs, cost of accommodation, travel, and food peritransplant and indirect costs such as lost wages for the patient and family members have not been included. | Table 1: Indications for autologous HSCT for the year 2017 at our center
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 | Table 2: Indications and types of donors for allogeneic HSCT for the year 2017 at our center
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 | Table 3: Data on total direct admission costs and the financial assistance availed for autologous and matched related donor HSCT for the year 2017 at our center
Click here to view |
| :: Strategies to Make HSCT More Cost-Effective | | |
Efforts are being made to introduce techniques, which can reduce costs of HSCT. These include innovative supportive care strategies and the use of information technology tools.[19],[24]
For developing countries, HSCT units can be initiated in clean single rooms and subsequently upgraded to rooms with high-efficiency particulate air filtration.[12],[25] Use of noncryopreserved grafts for autologous HSCT for lymphomas and myeloma is feasible and avoids the costs required for maintaining a cryopreservation facility.[26] However, practically, although this approach has almost become the norm for myeloma transplants in developing countries, the longer duration of conditioning in autologous HSCT for lymphomas makes cryopreservation desirable. In such cases, freezing at −80° is feasible and may obviate the need for controlled rate freezing which is much more costlier and requires high start-up costs.[27] Moreover, once the HSCT center attains large patient volumes, developing an in-house HLA and chimerism analysis laboratory can help to further reduce costs. The use of generic drugs can results in major cost savings in HSCT, provided necessary pharmacokinetic and efficacy data are available for these generic drugs.[28],[29] It is also important for centers to not just blindly follow western practices but adapt practices that would be more appropriate for Indian patients. Multiple studies from our center have helped in developing treosulfan-based regimens to improve outcomes in high-risk thalassemia as well as in identifying cost-effective regimens to reduce graft-versus-host disease in aplastic anemia.[30],[31]
In conclusion, although HSCT has come a long way in India over the last four decades, there are ample opportunities to improvise the technique to make it more accessible. Newer strategies need to be devised at multiple levels including at central and state government level, and at individual transplant center level to access financial support from charitable trusts to make HSCT a very cost-effective tool in curing Indian patients with a variety of hematological disorders.
Acknowledgments
We would like to thank our department social worker Mrs. Gomathi Joseph for her help in collecting the data on the direct cost of transplantation at our center.
| :: References | | |
| 1. | Majhail NS, Farnia SH, Carpenter PA, Champlin RE, Crawford S, Marks DI, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2015;21:1863-9.  |
| 2. | Younger DS. Health care in India. Neurol Clin 2016;34:1103-14. |
| 3. | Selvaraj S, Farooqui HH, Karan A. Quantifying the financial burden of households' out-of-pocket payments on medicines in India: A repeated cross-sectional analysis of national sample survey data, 1994-2014. BMJ Open 2018;8:e018020. |
| 4. | Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA, et al. Acute myeloid leukaemia: Challenges and real world data from India. Br J Haematol 2015;170:110-7. |
| 5. | Philip C, George B, Korula A, Srivastava A, Balasubramanian P, Mathews V. Treatment rates of paediatric acute myeloid leukaemia: A view from three tertiary centres in India-response to Gupta et al. Br J Haematol 2016;175:347-9. |
| 6. | Chandy M. Stem cell transplantation in India. Bone Marrow Transplant 2008;42(Suppl 1):S81-S84. |
| 7. | Colah R, Italia K, Gorakshakar A. Burden of thalassemia in India: The road map for control. Pediatric Hematol Oncol J 2017:79-84. |
| 8. | George B, Mathews V, Viswabandya A, Abraham A, Ganapule A, Fouzia NA, et al. Immunosuppressive therapy and bone marrow transplantation for aplastic anaemia--The CMC experience. J Assoc Physicians India 2015;63(3 Suppl):36-40. |
| 9. | Mahapatra M, Singh PK, Agarwal M, Prabhu M, Mishra P, Seth T, et al. Epidemiology, clinico-haematological profile and management of aplastic anaemia: AIIMS experience. J Assoc Physicians India 2015;63(3 Suppl):30-5. |
| 10. | Wood WA, Brazauskas R, Hu ZH, Abdel-Azim H, Ahmed IA, Aljurf M, et al. Country-level macroeconomic indicators predict early post-allogeneic hematopoietic cell transplantation survival in acute lymphoblastic leukemia: A CIBMTR analysis. Biol Blood Marrow Transplant 2018;24:1928-35. |
| 11. | |
| 12. | Hashmi SK, Srivastava A, Rasheed W, Adil S, Wu T, Jagasia M, et al. Cost and quality issues in establishing hematopoietic cell transplant program in developing countries. Hematol Oncol Stem Cell Ther 2017;10:167-72. |
| 13. | |
| 14. | |
| 15. | Gupta S, Madkaikar M, Singh S, Sehgal S. Primary immunodeficiencies in India: A perspective. Ann N Y Acad Sci 2012;1250:73-9. |
| 16. | Sharma SK, Choudhary D, Gupta N, Dhamija M, Khandelwal V, Kharya G, et al. Cost of hematopoietic stem cell transplantation in India. Mediterr J Hematol Infect Dis 2014;6:e2014046. |
| 17. | |
| 18. | Majhail NS, Mau LW, Denzen EM, Arneson TJ. Costs of autologous and allogeneic hematopoietic cell transplantation in the United States: A study using a large national private claims database. Bone Marrow Transplant 2013;48:294-300. |
| 19. | Chandy M. Innovative supportive care practices for stem cell transplantation in India. Biol Blood Marrow Transplant 2009;15(1 Suppl):95-8. |
| 20. | John MJ, Jyani G, Jindal A, Mashon RS, Mathew A, Kakkar S, et al. Cost effectiveness of hematopoietic stem cell transplantation compared with transfusion chelation for treatment of thalassemia major. Biol Blood Marrow Transplant 2018;24:2119-26. |
| 21. | Prinja S, Kaur G, Malhotra P, Jyani G, Ramachandran R, Bahuguna P, et al. Cost-effectiveness of autologous stem cell treatment as compared to conventional chemotherapy for treatment of multiple myeloma in India. Indian J Hematol Blood Transfus 2017;33:31-40. |
| 22. | |
| 23. | Mathews V, Balasubramanian P, Abraham A, George B, Srivastava A. Allogeneic stem cell transplantation for thalassemia major in India. Pediatric Hematol Oncol J 2017:114-20. |
| 24. | Agarwal RK, Sedai A, Dhimal S, Ankita K, Clemente L, Siddique S, et al. A prospective international cooperative information technology platform built using open-source tools for improving the access to and safety of bone marrow transplantation in low- and middle-income countries. J Am Med Inform Assoc 2014;21:1125-8. |
| 25. | Kumar R, Naithani R, Mishra P, Mahapatra M, Seth T, Dolai TK, et al. Allogeneic hematopoietic SCT performed in non-HEPA filter rooms: Initial experience from a single center in India. Bone Marrow Transplant 2009;43:115-9. |
| 26. | Kardduss-Urueta A, Gale RP, Gutierrez-Aguirre CH, Herrera-Rojas MA, Murrieta-Álvarez I, Perez-Fontalvo R, et al. Freezing the graft is not necessary for autotransplants for plasma cell myeloma and lymphomas. Bone Marrow Transplant 2018;53:457-60. |
| 27. | Detry G, Calvet L, Straetmans N, Cabrespine A, Ravoet C, Bay JO, et al. Impact of uncontrolled freezing and long-term storage of peripheral blood stemcells at -80 °C on haematopoietic recovery after autologous transplantatio. Report from two centres. Bone Marrow Transplant 2014;49:780-5. |
| 28. | Srivastava A, Mohanan E, Fouzia N, Panetta J, Lakshmi K, Korula A, et al. Pharmacokinetics of a generic treosulfan in patients with beta thalassemia major undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2017;23:S301-2. |
| 29. | Mohanan E, Royan S, Panetta J, Fouzia N, Korula A, Abraham A, et al. Generic intravenous busulfan in hematopoietic stem cell transplantation: Relevance of therapeutic drug monitoring. Abstract presented at the 57 th Annual Meeting and Exposition of the American Society of Hematology, Orlando, FL, USA, 2015. |
| 30. | Mohanan E, Royan S, Panetta J, Fouzia N, Korula A, Abraham A, et al. Generic intravenous busulfan in hematopoietic stem cell transplantation: Relevance of therapeutic drug monitoring. Abstract presented at the 57th Annual Meeting and Exposition of the American Society of Hematology. Orlando, FL, USA; 2015. |
| 31. | George B, Pn N, Devasia AJ, Kulkarni U, Korula A, Lakshmi KM, et al. Post-transplant cyclophosphamide as sole graft-versus-host disease prophylaxis is feasible in patients undergoing peripheral blood stem cell transplantation for severe aplastic anemia using matched sibling donors. Biol Blood Marrow Transplant 2018;24:494-500. |
[Table 1], [Table 2], [Table 3]
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