Hematopoietic cell transplantation landscape in India

Abstract

Hematopoietic cell transplantation (HCT), commonly known as Bone marrow transplantation (BMT), is a medical procedure used to treat various conditions, including blood cancers, genetic disorders, and certain autoimmune diseases. The procedure involves replacing damaged or diseased bone marrow with healthy stem cells to promote the production of new, healthy blood cells. In India, HCT has been performed for several years in specialized medical centers. India has a growing healthcare infrastructure, and many hospitals are equipped to perform these procedures. Though there are studies on HCTs done at individual transplant centers in India, a comprehensive analysis of the current landscape of HCT in the country is lacking. HCT in India has seen major advances both in the quantity and quality of HCT centers. This review article has attempted to cover the gaps of HCT in India, including its status in the Armed Forces HCT centers.

Since the first allogenic Hematopoietic Cell Transplant (HCT) done at Tata Memorial Hospital, Mumbai in 1983,¹ the HCT program in India has come a long way. There are 114 transplant centers in India as on 30th December 2022 with a total number of 26,843 transplants (1983–2022) as reflected in the Indian Society for Blood and Marrow Transplantation Registry (ISBMT). The scope for indications for HCT has been expanding over the last few decades. HCT has revolutionized the treatment of many, hitherto, incurable diseases and is offered for serious life-threatening conditions.² It has now become the standard of care for numerous benign and malignant diseases. Broad outlines regarding HCT was published in 2021 by ICMR as the national guideline for hematopoietic cell transplantation.³ It is one of the most complex (Fig. 1)² and demanding of medical therapies posing several challenges to the transplant physician and unit. However, there is a supply demand imbalance and the country needs many more HCT centers, both public and private.

Fig. 1.

Steps involved in allo-HCT. (HLA - Human leucocyte antigen, HSC -Haematopoietic stem cell, PBSC - Peripheral blood stem cell, BM- Bone marrow, UCB - Umbilical cord blood, TPN - Total parenteral nutrition).

Despite HCT being a well-established clinical practice, there was a gap in the distinction between its use for approved and unapproved indications. In order to address the concerns related to rampant use of stem cells for unapproved indications which posed a threat to the well-being of the vulnerable and diseased groups, Ministry of Health and Family Welfare (MoHFW) and NITI Aayog requested ICMR to formulate separate guidelines to bring about clarity for the stakeholders. As a result of this, the 2021 ICMR national guideline for hematopoietic cell transplantation was formulated.

The aim of the National Guidelines for Hematopoietic Cell Transplantation −2021 is to lay down a template and help transplant physicians and centers formulate their own protocols and policies to conduct HCT. In addition to this, ICMR has also published ‘Evidence-Based Use of Stem Cell Therapy in Human Diseases’ to address the experimental use of stem cells and assimilate available evidence in this nascent field. It covers a total of 11 conditions so far.⁴

Indications for HCT

The approved indications for HCT are listed in Table 1, Table 2 as adopted from EBMT.⁵

Table 1.

Approved Indications for HCT in India for adults (Adopted from EBMT).⁵

Disease	Disease status	MSD Allo	MUD Allo	MMAD Allo	Auto
Leukaemias
AML	CR1 (favourable risk and MRD−)	GNR/II	GNR/II	GNR/II	CO/I
	CR1 (favourable risk and MRD+)	CO/II	CO/II	CO/II	GNR/II
	CR1 (intermediate risk)	S/II	CO/II	CO/II	CO/I
	CR1 (adverse risk)	S/II	S/II	S/II	GNR/I
	CR2	S/II	S/II	S/II	CO/II
	APL molecular CR2	S/II	CO/II	GNR/III	S/II
	Relapse or refractory	CO/II	CO/II	CO/II	GNR/III
ALL	Ph (−), CR1 (standard risk and MRD−)	GNR/II	GNR/II	GNR/III	CO/III
	Ph (−), CR1 (standard risk and MRD+)	CO/II	CO/II	CO/II	GNR/II
	Ph (−), CR1 (high risk)	S/II	S/II	CO/II	GNR/III
	Ph (+), CR1 (MRD−)	S/II	S/II	CO/II	CO/III
	Ph (+), CR1 (MRD+)	S/II	S/II	S/II	GNR/II
	CR2	S/II	S/II	S/II	GNR/II
	Relapse or refractory	CO/II	CO/II	CO/II	GNR/III
CML	First CP, failing second- or thirdline TKI	S/II	S/II	CO/III	GNR/II
	Accelerated phase, blast crisis or > first CP	S/II	S/II	CO/II	GNR/III
Myelofibrosis	Primary or secondary with an intermediate or high DIPSS score	S/II	S/II	S/III	GNR/III
MDS	RA, RCMD, RAEB I and II	S/II	S/II	S/II	GNR/III
	sAML in CR1 or CR2	S/II	S/II	S/II	CO/II
	More advanced stages	S/II	S/II	S/II	GNR/III
CLL	Poor risk disease, not transformed	S/II	S/II	CO/III	GNR/III
	Richter's transformation	S/III	S/III	CO/III	CO/III
Lymphoid malignancies
DLBCL	CR1 (Intermediate/high IPI at dx)	GNR/III	GNR/III	GNR/III	CO/I
	Chemosensitive relapse, ≥CR2	CO/II	CO/II	D/III	S/I
	Chemosensitive relapse after auto- HCT failure	S/II	S/II	CO/III	GNR/III
	Refractory disease	CO/II	CO/II	CO/III	CO/II
	Primary CNS lymphoma	GNR/III	GNR/III	GNR/III	S/I
FL	CR1, untransformed	GNR/III	GNR/III	GNR/III	GNR/II
	CR1, transformed to high-grade lymphoma	GNR/III	GNR/III	GNR/III	CO/III
	Chemosensitive relapse, ≥CR2	CO/III	CO/III	GNR/III	S/II
	≥CR2 after auto-HCT failure	S/II	S/II	D/III	GNR/III
	Refractory	CO/II	CO/II	CO/III	GNR/III
MCL	CR1	GNR/III	GNR/III	GNR/III	S/I
	CR/PR > 1, no prior auto-HCT	CO/III	CO/III	D/III	S/II
	CR/PR > 1, after prior auto-HCT	S/II	S/II	CO/III	GNR/II
	Refractory	CO/II	CO/II	D/III	GNR/II
WM	CR1	GNR/III	GNR/III	GNR/III	GNR/III
	Chemosensitive relapse, ≥CR2	GNR/III	GNR/III	GNR/III	CO/II
	Poor risk disease	CO/II	CO/II	D/III	GNR/III
PTCL	CR1	CO/II	CO/II	GNR/III	CO/II
	Chemosensitive relapse, ≥CR2	S/II	S/II	CO/III	CO/II
	Refractory	CO/II	CO/II	CO/III	GNR/II
Primary CTCL	EORTC/ISCL stages I–IIA (Early)	GNR/III	GNR/III	GNR/III	GNR/III
	EORTC/ISCL stages IIB–IV (Advanced)	CO/III	CO/III	D/III	GNR/III
HL	CR1	GNR/III	GNR/III	GNR/III	GNR/I
	Chemosensitive relapse, no prior auto-HCT	D/III	D/III	GNR/III	S/I
	Chemosensitive relapse, after prior auto-HCT	S/II	S/II	CO/III	CO/III
	Refractory	D/II	D/II	D/III	CO/III
MM	Upfront standard risk	CO/II	CO/II	GNR/III	S/I
	Upfront high risk	S/III	S/III	CO/II	S/I
	Chemosensitive relapse, prior auto- HCT	CO/II	CO/II	CO/II	S/II
AL	CO/III	CO/III	GNR/III	CO/II	CO/III
Other diseases
Acquired SAA and AA/PNH	Newly diagnosed	S/II	CO/II	GNR/III	NA
	Relapsed/refractory	S/II	S/II	CO/II	NA
Haemolytic PNH		GNR/II	GNR/II	GNR/II	NA
Constitutional SAA		S/II	S/II	CO/II	NA
Breast Cancer	Adjuvant high risk, HER2 negative	GNR/III	GNR/III	GNR/III	CO/II
	Metastatic, chemosensitive	D/II	D/II	GNR/III	D/CO/II
Germ Cell Tumors	Second line, high risk	GNR/III	GNR/III	GNR/III	CO/II
	Primary refractory, second and further relapse	GNR/III	GNR/III	GNR/III	S/II
Ovarian Ca	High risk/recurrent	D/II	GNR/III	GNR/III	GNR/I
Medulloblastoma	Post-surgery, high risk	GNR/III	GNR/III	GNR/III	CO/III
Small cell lung Ca	Limited	GNR/III	GNR/III	GNR/III	D/II
Soft tissue Sa	Metastatic	D/III	GNR/III	GNR/III	GNR/II
Ewing's Sa	Locally advanced/metastatic, chemosensitive	D/III	GNR/III	GNR/III	CO/III
Renal cell Ca	Metastatic, cytokine-refractory	D/II	D/II	GNR/III	GNR/III
Multiple Sclerosis	Highly active RR-MS failing DMT	D/III	GNR/III	GNR/III	S/I
	Progressive MS with AIC, and aggressive MS	D/III	GNR/III	GNR/III	CO/II
Systemic sclerosis		D/III	GNR/III	GNR/III	S/I
SLE		D/III	GNR/III	GNR/III	CO/II
Crohn's disease		D/III	D/III	D/III	CO/II
Rheumatoid arthritis		D/III	GNR/III	GNR/III	CO/II
JIA		CO/II	CO/II	CO/III	CO/II
Monogenic AD		CO/II	CO/II	CO/III	GNR/II
Vasculitis		GNR/III	GNR/III	GNR/III	CO/II
PM-DM		GNR/III	GNR/III	GNR/III	CO/II
Autoimmune cytopenias		CO/II	CO/II	CO/III	CO/II
Neuromyelitis Optica		D/III	D/III	D/III	CO/II
CIDP, MG and SPS		GNR/III	GNR/III	GNR/III	CO/II
Type 1 diabetes		GNR/III	GNR/III	GNR/III	D/II
RCD type II		GNR/III	GNR/III	GNR/III	CO/II
Primary ID		CO/II	CO/II	CO/II	NA

Abbreviations: AA aplastic anemia, AD autoimmune disorders, AIC active inflammatory component, AL amyloidosis, ALL acute lymphoblastic leukaemia, Allo allogeneic transplantation, AML acute myeloid leukaemia, APL acute promyelocytic leukaemia, Auto autologous transplantation, Ca cancer or carcinoma, CIDP chronic inflammatory demyelinating polyneuropathy, CLL chronic lymphocytic leukaemia, CML chronic myelogenous leukaemia, CNS central nervous system, CO clinical option (can be carried after careful assessment of risks and benefits), CP chronic phase, CR1, 2, 3 first, second, third complete remission, CTCL cutaneous T cell lymphoma, D developmental (further trials are needed), DIPSS Dynamic International Prognostic Score System, DLBCL diffuse large B cell lymphoma, DMT disease-modifying treatments, FL follicular lymphoma, GNR generally not recommended, HL Hodgkin lymphoma, HCT haematopoietic stem cell transplantation, ID immunodeficiency, IPI International Prognostic Index, JIA juvenile idiopathic arthritis, MCL mantle cell lymphoma, MDS myelodysplastic syndromes, MG myasthenia gravis, MM multiple myeloma, MMAD mismatched alternative donors (cord blood, haploidentical and mismatched unrelated donors), MRD minimal residual disease, MS multiple sclerosis, MSD matched sibling donor, MUD well-matched unrelated donor (8/8, 10/10 or 9/10 if mismatched is in DQB1), NA not applicable, PM-DM polymyositis-dermatomyositis, PNH paroxysmal nocturnal hemoglobinuria, PR partial remission, RA refractory anemia, RAEB refractory anemia with excess blasts, RCD refractory coeliac disease, RCMD refractory cytopenia with multilineage dysplasia, RR-MS relapsing–remitting multiple sclerosis, S standard of care (generally indicated in suitable patients), Sa sarcoma, SAA severe aplastic anemia, sAML secondary acute myeloid leukaemia, SLE systemic lupus erythematosus, SPS stiff person syndrome, TCL T cell lymphoma, TKI tyrosine kinase inhibitors, WM Waldenström macroglobulinemia.

Table 2.

Approved indications for HCT in India for children and adolescents (adopted from EBMT).⁵

Disease	Disease status	MSD Allo	MUD Allo	MMAD Allo	Auto
Hematological malignancies
AML	CR1 (low risk) CR1 (high and very high risk) CR2 >CR2	GNR/II S/II S/II S/II	GNR/II S/II S/II CO/II	GNR/III CO/II S/II CO/II	GNR/II GNR/II GNR/II GNR/II
ALL	CR1 (low risk) CR1 (high risk) CR2 >CR2	GNR/II S/II S/II S/II	GNR/II S/II S/II S/II	GNR/III CO/II CO/II CO/II	GNR/II GNR/II GNR/II GNR/II
CML	First CP, failing second- or third-line TKI Accelerated phase, blast crisis or > first CP	S/II S/II	S/II S/II	CO/II CO/II	GNR/III GNR/III
MDS and JMML		S/II	S/II	CO/III	GNR/III
NHL	CR1 (low risk) CR1 (high risk) CR2	GNR/II CO/II S/II	GNR/II CO/II S/II	GNR/II CO/II CO/II	GNR/II CO/II CO/II
HL	CR1 First relapse, CR2	GNR/II CO/II	GNR/II CO/III	GNR/II CO/III	GNR/II S/II
Non-malignant disorders and solid tumours
Primary ID	Severe combined ID Other primary ID	S/II S/II	S/II S/II	S/II CO/II	NA NA
MPS	MPS-1H Hurler MPS-1H Hurler Scheie (severe) MPS-VI Maroteaux-Lamy	S/II GNR/III CO/II	S/II GNR/III CO/II	CO/II GNR/III CO/II	NA NA NA
Thalassemia and SCD		S/II	CO/II	CO/II	NA
Osteopetrosis		S/II	S/II	S/II	NA
Acquired SAA		S/II	S/II	CO/II	NA
IBMFS		S/II	S/II	CO/II	NA
Germ cell tumours		CO/II	CO/II	CO/II	CO/II
Sarcoma	Ewing's sarcoma (high risk or > CR1)	D/II	D/III	D/III	S/II
	Soft tissue sarcoma (high risk or > CR1)	D/II	D/II	D/III	CO/II
	Osteogenic sarcoma	GNR/III	GNR/III	GNR/III	D/II
	Ewing's sarcoma (high risk or > CR1)	D/II	D/III	D/III	S/II
Neuroblastoma	High risk or > CR1	CO/II	CO/II	D/III	S/II
Brain tumours		GNR/III	GNR/III	GNR/III	CO/II
Wilms' tumour	>CR1	GNR/III	GNR/III	GNR/III	CO/II
AD	Including monogenic AD	CO/II	CO/II	CO/II	CO/II

Abbreviations: AD autoimmune disorders, ALL acute lymphoblastic leukaemia, Allo allogeneic transplantation, AML acute myeloid leukaemia, Auto autologous transplantation, CML chronic myelogenous leukaemia, CO clinical option (can be carried after careful assessment of risks and benefits), CR1, 2 first, second complete remission, D developmental (further trials are needed), GNR generally not recommended, HL Hodgkin lymphoma, HCT haematopoietic stem cell transplantation, IBMFS inborn marrow failure syndromes (Fanconi anemia, dyskeratosis congenita, Blackfan–Diamond anemia and others), ID immunodeficiency, JMML juvenile myelomonocytic leukaemia, MDS myelodysplastic syndromes, MMAD mismatched alternative donors (cord blood, haploidentical and mismatched unrelated donors), MPS mucopolysaccharidosis, MSD matched sibling donor, MUD well-matched unrelated donor (8/8, 10/10 or 9/10 if mismatched is in DQB1), S standard of care (generally indicated in suitable patients), SAA severe aplastic anemia, SCD sickle cell disease (high risk).

Establishing transplant centres in India

In India, HCT is offered by four major types of hospitals namely government, corporate, Armed forces and not-for-profit trust hospitals. The 2021 ICMR National Guideline for Hematopoietic Cell Transplantation has laid out the minimum criteria in terms of patient volume, infrastructure and facilities, transplant personnel, academic qualifications, documentation, and data management, for the safe and successful performance of HCT. Whereas, the Worldwide Networks for Blood and Marrow Transplantation has laid down a four-tier requirement in establishing HCT centers (absolute minimum, minimum, preferred, and ideal).⁶ It also addresses the clinical, technical, and financial considerations in resource-limited settings of developing countries. In India, accreditation of transplant centers is yet to be put in place as there is no agency undertaking this task presently.

A good blood bank with routine blood banking services, apheresis facility and component support are needed, as well as the availability of leuko-reduced and irradiated products to avoid the risk of transfusion associated GVHD in severely immunosuppressed HCT recipients.⁶ Protocols for cryopreservation and management of ABO incompatibility, air handling, and air quality monitoring should be in place. The transplant unit should have a radiotherapy unit with provision to perform TBI, in its proximity. In the case of centers performing allogenic HCT, access to NABL certified histocompatibility laboratory is necessary.

High-quality laboratory support including hematology, biochemistry, pathology, bacteriology, virology, mycology and imaging support (Radiodiagnosis, CT scans and interventional radiology) should be available round-the-clock. Provisions for ICU, dialysis, and bronchoscopy for both adults and children should be available within the institution. A pharmacy well equipped with chemotherapeutic drugs, antiemetics, and antibiotics should be available within the center.⁶

The HCT center should have transplant physicians, transplant nurses, resident medical personnel, dietician, and pharmacist. The transplant physician should have the certified and requisite training as listed in the National guideline for HCT.³ The transplant nurse-to-patient ratio should not exceed 1:2. Nursing staff should be trained in handling chemotherapy and infection control. Pharmacists should be well-versed with chemotherapeutic drugs, antiemetics, and antibiotics.⁶ Training of transplant coordinators, apheresis technicians, and data management teams is also vital.

Training of transplant personnel

As on date, there are 30 centers offering a 03 – year course in Clinical Hematology, with a total of 65 seats. DM Clinical Hematology is conducted in 13 centers (36 seats), and DrNB Clinical Hematology in 17 centers (29 seats), where formal training in hematology and HCT is mandated. Few other centers also offer fellowship courses in HCT. It is crucial that more centers should take up training of transplant personnel in order to expand and ensure the quality of the HCT program in the country.

Running HCT centers in India

Once the HCT unit is well established and grows or embarks on complex procedures, the preferred requirements⁶ like additional trained staff, an outpatient clinic with dedicated infusion rooms, and supporting staff like a dedicated transplant coordinator and social worker are necessary. Efforts should be made to obtain government support for the registration of new programs and support for data collection and reporting.

An important factor that needs to be addressed in running an HCT program in resource-constrained settings in India is cost-effectiveness and cost-utility. The Worldwide Networks for Blood and Marrow Transplantation has made important recommendations in this regard. Evidence of both clinical and economic effectiveness is important for developing a cost-containment program before adopting new technologies.⁷ The major determinants of the cost establishment of an HCT program are patient-related factors, graft source and donor type, cost of drugs, laboratory service and radiology, technology and quality, and supportive care.⁸

Studies have also confirmed that compared to high-intensity conditioning regimens and myeloablative regimens, the reduced-intensity conditioning regimens are associated with lower costs and fewer median hospital stays within the first-year post-transplant.⁹

In India, PBSCs are being increasingly used with good outcomes in various transplant settings, though it is associated with a higher incidence of chronic GVHD (Fig. 2)² Drugs and pharmacy accounts for 8%–39% of the total expenditure in HCTs⁸; hence using generic drugs or biosimilars with proven efficacy may help reduce this cost. Priority should also be given to shorten the time from diagnosis to HCT.

Fig. 2.

Scleroderma like skin and oral lesions due to chronic GvHD in a patient after allo-HCT (PBSC) for CML.

Transplant registries in India

Nearly 60–70% of patients requiring HCT will not have a fully matched related family donor.³ The first registry in the world was established in 1974 called the Anthony Nolan Bone Marrow Registry, established by the mother of Anthony Nolan, who suffered from Wiskott-Aldrich Syndrome. Bone marrow donors worldwide (BMDW) was established in 1988 at Leiden, Netherlands, and has >60 registries from over 45 countries globally with >30 million donors and over 720,000 cord blood units registered.¹⁰

The Indian registries included DATRI (blood stem cell donors registry) Chennai, Jeevan Blood Bank Chennai, SCRI-BMST (Bangalore Medical Services Trust), Bangalore, MDRI (Marrow Donor Registry India) Mumbai, BMCDT-BMR (Medical College Alumni) Bangalore, GENE BANDHU (Bharat Stem Cells) New Delhi, and the Arjan Vir Foundation Delhi, which have a total of more than 500,000 voluntary donors.³

Studies on HCT in India

The outcomes of HCTs for various indications from various centers in India have been summarised in Table 3^{11, 12, 13, 14, 15, 16} and Table 4.^{17, 18, 19, 20, 21}

Table 3.

Outcome of HCTs in Adults from various centers in India.

	Ganapule et al. 11	Kulkarni et al. 12	Kumar et al.13	Kumar et al.14	Sharma et al.15	Nair et al.16
Institute	CMC Vellore	CMC Vellore	AIIMS, New Delhi	Army Hospital Research&Referral, New Delhi	BLK Superspeciality Hospital, New Delhi	Army Hospital Research & Referral, New Delhi
N	254	245	349	702 (Total) 188 (Pediatric) 514 (Adult)	516	119
Type of HCT
Autologous	0	245	349	297	258	0
Allogenic	254	0	0	405	258	119
Indication
Autologous∖1	NA	Multiple Myeloma	Multiple Myeloma	Multiple Myeloma Hodgkin Lymphoma Non-Hodgkin Lymphoma	Multiple myeloma Non-Hodgkin lymphoma Hodgkin lymphoma ALL	NA
Allogenic∖1	AML	NA	NA	AML Aplastic Anema ALL, CML MDS, PID	AML	AML, ALL CML, JMML Thalassemia Major Acquired SAA MDS, PNH
Median age of patients (in years)				09 (Pediatric)
Autologous∖1	NA	51	52	42 (Adult)	43	NA
Allogenic	34	NA	NA	(Both autologous and allogenic combined)	NA	17
Median neutrophil engraftment day
Autologous	NA	12	NR	NR	NA	NA
Allogenic	NR	NA	NA	NR	NA	11.3
Median follow-up period	NA (Retrospective study)	40.7 months	73 months	NA (Retrospective study)	NA	34 months
OS				65% (Both autologous and allogenic combined)
Autologous	NA	61.6% ± 3.8%	63.2% (5-year OS)		69.75 (5-year OS)	NA
Allogenic	40.1 ± 3.5% (5-year OS)	NA	NA		47.0% (5-year OS)	62.3%
PFS/EFS
Autologous HCT	NA	37.2% ± 3.9%	38.5% (5 years)	NR	32.5% (5-year DFS)	NA
Allogenic HCT	38.7 ± 3.4% (5-year DFS)	NA	NA		41.8% (5-year DFS)	NR
TRM
Autologous HCT	NA	2.86%	7.2%	NR		NA
Allogenic HCT	50.8% (1-year TRM)	NA	NA		30.8% (Overall mortality)	37.7% (Overall mortality)

Table 4.

Outcome of HCTs in Pediatric population from various centers in India.

	Raj et al.17	Doval et al.18	Batra et al.19	Arora et al.20	Velu Nair et al. 21 (HCT for Genetic disorders)
Institute	Multicentric study	BLK Superspeciality Hospital, New Delhi	Adyar cancer institute, Chennai	Dr. Brairch, AIIMS, New Delhi	Army Hospital Research&Referral, New Delhi
N	228	20	21	46	17
Type of HCT
Autologous	NA	0	0	0	0
Allogenic	228	23	21 (haploidentical)	46	19
Indication
Autologous	NA	NA	NA	NA	NA
Allogenic	SCID HLH Wiskott Aldrich Syndrome Chronic Granulomatous Disease	Fanconi anemia	AML CML	AML	Thalassemia major Diamond Blackfan anemia Fanconi anemia, Congenital dyserythropoietic anemia
Median age of patients (in years)
Autologous	NA	NA	NA	NA	NA
Allogenic	12 months	09	15	10.7	07
Median engraftment day
Autologous	NA	NA	NA	NA	NA
Allogenic	NR	11	14	12	13
Median follow-up period	14.4 Months	23 months	26 months	15.6 months	36 Months
OS					NR
Autologous	NA	NA	NA	NA
Allogenic	68%	65%	38%	36%
DFS
Autologous HCT	NA	NA	NA	NA	NA
Allogenic HCT	53.3%	50%	42.8%	33%	77%
TRM
Autologous HCT	NA	NA	NA	NA	NA
Allogenic HCT	27%	30%	38%	2.2%	23%

Current activity of HCT centers in India

After a hiatus of about two decades from the establishment of the first BMT center in India, there has been phenomenal growth in the number of HCT centers in the country over the past decade. Currently, there are 114 HCT centers in the country of which 89 are reporting to the ISBMT registry. The total number of transplants reported is 26,843 (1983–2022), out of which 15,677 were allogenic and 11,166 were autologous HCT, and 80.96% of these have been performed between 2012 and 2022 (ISBMT data), which is mainly attributed to a steep increase in the number of HCT units during this period. Among these, pediatric HCTs constitute 35.9% and adult HCTs amount to 64%.

Among the allogenic transplants, 66.45% were MRD, 8.64% were MUD and 24.89% were Haploidentical HCTs. There has been a steady increase in the number of haploidentical transplants done in the past decade. The most common indications for HCT overall were Multiple Myeloma (23%), AML (14%), and Thalassemia (12%). The top three indications for autologous HCT (both adult and pediatric populations combined), were Multiple Myeloma (54%), Hodgkin Lymphoma (16%), and Non-Hodgkin Lymphoma (11%), whereas the major indications for allogenic HCT were AML (22%), Thalassemia (20%), Bone Marrow failure syndrome (15%) and ALL (15%). In pediatric population, the most common indications for allogenic HCT were Thalassemia (35%), ALL (15%) and bone marrow failure syndromes (13%), and the major indications for autologous HCTs were Neuroblastoma (38%) and Hodgkin Lymphoma (29%) (ISBMT data).

HCT in Armed Forces centers

The transplant program in the Armed Forces was initiated in 1998 in Army Hospital (Research & Referral) wherein, transplants were done in clean, non-HEPA filtered rooms. A new 03 bedded HEPA filtered unit was operational from early 2002²² and since then a total of 702 transplants have been done in this unit.¹⁴ A wide array of indications for HCT has been carried out in this center, both autologous and allogenic using stem cell sources from the bone marrow, peripheral blood and umbilical cord blood (UB) in both adults and pediatric patients. The transplant outcomes in both autologous and allogenic have been comparable with national and international HCT outcome data.

In the last two decades, HCT centers have also been set up in Command Hospital (Southern Command)/AFMC Pune; Command Hospital (Eastern Command) Kolkata; Command Hospital (Central Command) Lucknow; INHS Asvini Mumbai and Command Hospital Air Force Bangalore, which are all teaching hospitals running post graduate programs. Command Hospital (Southern Command)/ AFMC and AH (R&R) also conduct DM/DrNB/MCh courses in various subjects. Today, Armed Forces has one of the largest networks of trained transplant physicians, nurses, paramedical staff and technicians in the country. We also run DrNB course in Clinical Hematology (with HCT) in AH (R&R). Importantly, 135 service hospitals, have a very robust referral system, wherein, within a very short time, cases requiring HCT are referred to the appropriate tertiary care centers in their respective zones.

There is a significant emphasis to sensitize all post graduates to the nuances of clinical hematology and HCT in various Armed Forces teaching hospitals.

The unmet needs

A significant gap still exists between the projected need for HCT in the country as per the disease prevalence versus the actual number of HCTs performed.¹ A delay in referring the cases to tertiary care centers results in a negative impact on HCT outcomes. A major barrier to the accessibility of HCT in India is the cost factor. Support from government agencies and health coverage via government schemes can make a wide impact in this aspect.

Another challenge is the availability of donors for HCT. Only 30% of patients will have an HLA-matched sibling or related donor.³ Therefore, it is important that large donor registries are set up in India with access to a large number of voluntary donors.

The other major challenges include dealing with multidrug antimicrobial resistance and lack of collaborative clinical trials. The North East part of India is one region where HCT programs need to be augmented and supported.²³ Patients from this region must travel out of the state or resort to non-transplant options in these states. Hence efforts should be made to cover neglected regions when the HCT program should be expanded. Last but not the least, the cost for HCT should be brought down by using generic/biosimilar drugs and subsidies from central, state governments and other agencies.

The future of HCT in India

Haploidentical transplant programs are likely to expand further, mainly due to the logistic constraints in the country. This will lead to a reduction in the number of MUD and umbilical cord blood transplants. Application of novel targeted agents to achieve MRD negativity before transplant in AML, ALL, Multiple Myeloma, and CLL will improve the transplant outcomes,²⁴ though novel targeted agents can be a major limiting factor. Cellular therapy including Donor Lymphocyte Infusion and cell manipulation will go a long way in decreasing the frequency of GVHD while retaining Graft versus tumor effects.

Disclosure of competing interest

The authors have none to declare.