Primary immunodeficiencies (PIDs), recently reclassified as inborn errors of immunity (IEIs), represent a heterogeneous group of over 500 genetically defined disorders that impair the development or function of the immune system. Although individually rare, collectively they have a significant global health impact, contributing to recurrent infections, autoimmunity, autoinflammation, allergy, and malignancy. Advances in next-generation sequencing and immunological profiling have expanded the diagnostic landscape, enabling earlier recognition of atypical presentations and novel disease entities. Nevertheless, delayed diagnosis remains a challenge, particularly in low- and middle-income countries, where access to specialized testing and therapies is limited. Clinically, PIDs are diverse and may manifest from infancy to adulthood, often with overlapping phenotypes. The classical presentation of severe, recurrent, or unusual infections is increasingly recognized to be accompanied by immune dysregulation, including cytopenia, lymphoproliferation, and organ-specific autoimmunity. Early identification is essential, as timely interventions such as immunoglobulin replacement, antimicrobial prophylaxis, hematopoietic stem cell transplantation, and targeted biologic therapies significantly improve outcomes. This article provides an overview of the evolving understanding of PIDs, highlighting their clinical spectrum, diagnostic strategies, and therapeutic advances. By raising awareness among clinicians and health systems, it aims to reduce diagnostic delays and optimize patient care. Greater integration of molecular diagnostics, registries, and international collaboration is key to advancing precision medicine in the field of primary immunodeficiencies.
Keywords: Primary Immunodeficiency Diseases, Inborn Errors of Immunity, T cell defect.
Introduction
Hematopoietic
stem cell transplantation (HSCT) is a potentially curative treatment for a wide
range of malignant and non-malignant hematologic disorders, including
leukemias, thalassemia, aplastic anemia, and hemoglobinopathies1,2.
However, access to transplant facilities in India remains highly skewed toward
metropolitan areas and private sector hospitals, leaving large populations in
tier-2 and tier-3 cities without affordable access3,4.
Recognizing
this gap, the Department of Pediatrics at NSCB Medical College, Jabalpur,
initiated the development of a government-supported pediatric bone marrow
transplant (BMT) unit in early 2023. Located in central India, the institution
serves as a tertiary referral center catering to Madhya Pradesh and neighboring
states.
The objectives
were to:
This article
describes the planning, establishment, and operationalization of the unit and
presents outcomes of the first four transplants performed, highlighting the
feasibility of setting up BMT programs in government medical colleges with
structured planning and phased implementation.
Methods
1. Planning and Approval
Process
The initial
planning began in February 2023 when a detailed proposal outlining the
clinical need, infrastructure design, and projected costs was submitted to the
state health authorities. The proposal was approved the same year, with a
sanctioned budget of ₹8 crore—₹5 crore
allocated for infrastructure development and ₹3 crore for procurement of essential
medical equipment. The funding was released in phases, allowing progressive
construction and commissioning of the unit.
2. Infrastructure and
Design
A dedicated
area within the pediatric block was identified and remodeled according to
transplant-specific architectural and infection-control standards. The BMT
unit comprises 10 single-occupancy HEPA-filtered isolation rooms, each
equipped with:
An adjoining procedure
and apheresis room was established with installation of a cell separator
machine, biosafety cabinets, and appropriate sterilization facilities. A central
nursing observation area was integrated to allow continuous monitoring of
all patients.
3. Blood Bank Upgradation
Parallel to
unit development, the blood bank was upgraded to support
transplant-specific requirements.
4. Equipment Procurement
Essential
equipment procured included:
5. Human Resource
Development and Training
To ensure
sustainability, both clinical and technical staffs were trained prior to unit
commissioning.
6. Laboratory and
Diagnostic Collaborations
To minimize
cost and dependence on private agencies, a hub-and-spoke laboratory model
was implemented:
7. Infection Control
Measures
Comprehensive
infection control protocols were established, covering:
8. Patient Selection and
Conditioning Regimens
Patients were
selected after multidisciplinary review and family counseling. Donor selection
followed standard HLA typing.
9. Post-Transplant
Monitoring
Patients were
monitored daily for engraftment, infection, GVHD, and organ toxicities.
Results
Between March
and September 2025, four HSCTs were performed—two allogeneic and two
autologous. All patients achieved hematologic recovery and were discharged in
stable condition. A summary of cases and outcomes is shown in Table 1 (excluded
from word count).
Case 1:
Haploidentical Allogeneic HSCT for Refractory AML (FLT3⁺)
A 9-year-old girl with refractory AML, persistent MRD positivity after multiple
salvage therapies (Sorafenib along with 3+7 induction, one cycle of FLAG-Ida,
and four cycles of Venetoclax–Azacitidine), underwent haploidentical HSCT using
her mother as a 6/10 HLA-matched donor. Conditioning included Flu-Bu-Cy-ATG
with PTCy, CSA, and MMF prophylaxis. The bone marrow graft (6×10⁶ CD34⁺ cells/kg)
engrafted for neutrophils on day +20. She had delayed thrombocytopenia but
remained afebrile and was discharged on day +34
Case 2: Matched
Sibling HSCT for Sickle Cell Disease
A 5-year-old boy with transfusion-dependent sickle cell disease and recurrent
vaso-occlusive crises underwent HSCT using his 14-year-old HLA-matched sister
(12/12 match) as donor. Conditioning with Thio-Treo-Flu-ATG was followed by
PBSC infusion (4.8×10⁶ CD34⁺/kg). Engraftment for both neutrophils and platelets occurred on day
+12. Apart from transient febrile episodes during engraftment, his course was
uneventful. Chimerism at day +30 showed 100% donor cells. He was discharged in
stable condition.
Case 3:
Autologous HSCT for High-Risk Neuroblastoma
A 4-year-old boy with suprarenal neuroblastoma, post-COJEC chemotherapy and
radiotherapy, underwent autologous HSCT with Flu-Bu-Mel conditioning. Stem
cells were cryopreserved for 72 hours with 98% post-thaw viability (4×10⁶ CD34⁺/kg).
Engraftment occurred by day +13, and he was discharged on day +30 .
Case 4:
Autologous HSCT for High-Risk Neuroblastoma
A 3-year-old boy post-COJEC chemotherapy underwent autologous HSCT with
glycated Flu-Bu-Mel conditioning. Engraftment occurred on day +10, with minor
upper respiratory infection managed conservatively. He was discharged on day
+32 .
There were no
transplant-related mortalities. Median duration to ANC recovery was 13 days
(range 10–20), and median hospital stay was 31 days (24–34). All patients
remain on regular follow-up with stable counts.
Discussion
The experience
from NSCB Medical College demonstrates the feasibility of developing a BMT unit
within a government institution in a tier-2 city through strategic planning,
phased investment, and human resource development.
Infrastructure and
Infection Control
Adequate
infrastructure and infection control are essential for transplant success.
Previous Indian studies emphasize that infection control measures, especially
HEPA filtration and positive-pressure environments, significantly reduce
nosocomial infections and transplant-related mortality5,6. By
incorporating these standards, our unit maintained aseptic conditions equivalent
to private centers.
Training and Manpower
Developing
skilled human resources is the cornerstone of any new transplant program. Our
model of deputing nurses and technicians for short-term intensive training
mirrors approaches adopted by AIIMS, Delhi, and CMC Vellore7,8.
Continuous in-house education and mock drills further reinforced staff
confidence and procedural uniformity.
Collaborations and Resource
Optimization
Partnerships
with ICMR laboratories and NGOs proved vital. The hub-and-spoke model
reduced dependency on costly private facilities, ensuring cost-effective access
to molecular testing and chimerism analysis. Such collaborative frameworks have
been recommended by the Indian Society for Blood and Marrow Transplantation
(ISBMT) to scale transplant capacity in government sectors9.
Cost and Sustainability
Financial
constraints remain a major barrier in low- and middle-income countries (LMICs).
Even with state support, the average per-transplant cost was ₹4–5 lakh for
allogeneic and 3-4 lakh for Autologous Transplant, consistent with national estimates10,11. Integration with
government health schemes and NGO donations ensured that families incurred no
out-of-pocket expenses. However, sustainability requires dedicated
BMT-specific budget lines, bulk procurement of essential drugs, and a
central funding mechanism for investigations—each transplant needing
approximately ₹5 lakh for medications and disposables.
Clinical Outcomes
All four
patients in our initial cohort engrafted successfully without mortality—an
encouraging finding comparable with early outcomes from mature Indian centers
reporting survival rates of 85–95% in pediatric HSCT12,13. As
summarized in Table II, these early results from our center align with
national benchmarks and indicate that, despite a small sample size, the new
unit has achieved clinical safety and operational readiness. Though our sample
size is small, these results validate the clinical safety and readiness of the
new unit.
Challenges and Future
Directions
Challenges
encountered included delays in specialized tests due to lack of in-house flow
cytometry and the limited number of trained staff. Addressing these through equipment
expansion, staff recruitment, and training fellowships is
planned. In the long term, we aim to expand to 20 beds and initiate unrelated
donor transplants, CAR-T collaborations and gene therapy for benign genetic
diseases mainly hemoglobinopathies.
Conclusion
The
establishment of a fully functional pediatric bone marrow transplant unit at NSCB
Medical College, Jabalpur, within a government framework, demonstrates that
advanced hematologic therapies can be effectively decentralized beyond metro
cities. Strategic state funding, targeted manpower training, and
inter-institutional collaborations enabled successful early transplants with
favorable outcomes.
To sustain and
expand such programs, it is imperative for government policy to:
With structured
planning and state commitment, regional government medical colleges can evolve
into centers of excellence for HSCT, ensuring equitable access to
curative therapies for children across India.
References