Stem Cell Therapy in India and UAE | Complete Patient Guide

• IDEAL CANDIDATES — HAEMATOLOGICAL MALIGNANCIES:

• Acute Myeloid Leukaemia (AML) in first or second complete remission (CR1/CR2), particularly intermediate- or high-risk cytogenetics per ELN 2022 classification

• Acute Lymphoblastic Leukaemia (ALL) in CR1 (high-risk features: Philadelphia chromosome-positive [Ph+], MRD-positive) or CR2

• Hodgkin Lymphoma relapsed/refractory after ≥2 lines of therapy, eligible for autologous HSCT

• Diffuse Large B-Cell Lymphoma (DLBCL) and other aggressive non-Hodgkin lymphomas in chemosensitive relapse

• Multiple Myeloma: newly diagnosed patients aged <70 with adequate organ function, eligible for autologous tandem or single transplant after induction with VRd (bortezomib, lenalidomide, dexamethasone) or Dara-VRd

• Myelodysplastic Syndrome (MDS): IPSS-R score Intermediate-2 or High

• Chronic Myeloid Leukaemia (CML): blast phase or TKI-refractory chronic phase

• IDEAL CANDIDATES — NON-MALIGNANT DISORDERS:

• Severe Aplastic Anaemia (SAA): age <40 with HLA-matched sibling donor; older patients or MUD considered after ATG failure

• Sickle Cell Disease (HbSS): recurrent vaso-occlusive crises, stroke, or acute chest syndrome; best outcomes in paediatric/young adult patients

• Beta-Thalassaemia Major (Pesaro Class I–II): transfusion-dependent, younger patients with low iron burden and no hepatomegaly

• SCID and other primary immunodeficiencies

• Autoimmune conditions (MS, systemic sclerosis, Crohn's disease): HSCT or MSC therapy in refractory cases per clinical trial protocols

• REQUIRED DIAGNOSTIC WORKUP:

• HLA typing: high-resolution A, B, C, DRB1, DQB1 (10-locus) for patient and potential donors

• Bone marrow trephine biopsy and aspirate with cytogenetics, FISH, and molecular panel (FLT3, NPM1, IDH1/2, BCR-ABL, MRD by flow cytometry or PCR)

• PET-CT scan (for lymphoma staging and chemosensitivity assessment) or CT-CAP

• 2D Echocardiogram (LVEF must be ≥ 45% for most protocols)

• Pulmonary Function Tests (DLCO ≥ 40% predicted for BEAM-conditioning)

• Renal function (eGFR ≥ 30 mL/min), hepatic function (no cirrhosis; bilirubin < 2× ULN)

• Infectious serology: CMV IgG/IgM, EBV, HSV, VZV, HBsAg, Anti-HBc, Anti-HCV, HIV 1&2, HTLV-1

• Dental clearance (active infection is a contraindication)

• Fertility counselling and sperm/oocyte cryopreservation offered pre-conditioning

• RELATIVE AND ABSOLUTE CONTRAINDICATIONS:

• LVEF < 40% (absolute contraindication for myeloablative regimens)

• DLCO < 40% predicted (absolute for BEAM)

• Active uncontrolled infection (bacterial, fungal, or viral)

• Bilirubin > 3× ULN or active hepatic veno-occlusive disease (SOS/VOD)

• Creatinine > 2.5 mg/dL (relative; reduced-intensity regimens may be considered)

• Karnofsky Performance Score (KPS) < 60% or ECOG PS ≥ 3

• Active, uncontrolled malignancy not responsive to induction (chemo-refractory disease is a relative contraindication for allogeneic HSCT)

• Uncontrolled psychiatric illness that would prevent compliance with prolonged isolation protocols

AUTOLOGOUS HAEMATOPOIETIC STEM CELL TRANSPLANTATION (Auto-HSCT):

In autologous transplantation, the patient's own peripheral blood stem cells (PBSCs) are mobilised using G-CSF (filgrastim or plerixafor combination for poor mobilisers), collected via apheresis, and cryopreserved. Following high-dose conditioning chemotherapy (e.g., BEAM for lymphoma; high-dose melphalan 200 mg/m² for myeloma), the stored cells are thawed and re-infused. Because the graft is self-derived, there is no GvHD risk, enabling faster recovery (typical engraftment by Day +10 to +14). Auto-HSCT is the standard of care for eligible multiple myeloma and chemosensitive relapsed lymphoma patients. Tandem autologous transplantation (two sequential auto-HSCT within 6 months) is an option for high-risk myeloma. Modern centres use COBE Spectra or Spectra Optia apheresis systems with CD34+ cell count targets of ≥ 2×10⁶/kg (minimum) and ≥ 5×10⁶/kg (optimal).

ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION (Allo-HSCT):

Allogeneic transplantation uses stem cells from a related (sibling, parent, child) or unrelated matched donor, conferring the therapeutic graft-versus-tumour (GvT) effect crucial for leukaemia eradication. Donor sources include:

• Matched Sibling Donor (MSD): gold standard; ~25–30% probability of a fully matched sibling.

• Matched Unrelated Donor (MUD): sourced via international registries (DKMS, NMDP, Anthony Nolan); requires ≥ 9/10 HLA allele match.

• Haploidentical (Haplo) Transplant: uses a 50% HLA-matched family member (parent, sibling, child); now feasible with post-transplant cyclophosphamide (PTCy) GvHD prophylaxis (Baltimore/O'Donnell protocol), making it available to >95% of patients without a matched donor.

• Umbilical Cord Blood (UCB) Transplant: particularly useful in paediatric patients; requires lower cell dose thresholds.

CONDITIONING REGIMEN SELECTION:

• Myeloablative Conditioning (MAC): BuCy (busulfan IV + cyclophosphamide) or TBI-Cy (total body irradiation + cyclophosphamide). Used in younger patients (< 50–55 years) with good organ function; offers the lowest relapse rate.

• Reduced-Intensity Conditioning (RIC): Fludarabine + Busulfan (FluBu2) or Fludarabine + Melphalan. Used for older patients (≥ 55 years) or those with comorbidities; relies more on GvT effect than cytoreduction.

• Non-Myeloablative (NMA): Minimal cytoreduction; primarily immunosuppressive; suitable for frail or heavily pre-treated patients.

CELLULAR THERAPIES — BEYOND CONVENTIONAL HSCT:

• CAR-T Cell Therapy (Chimeric Antigen Receptor T-cell): Autologous T-cells are genetically engineered ex vivo to express a chimeric receptor targeting tumour antigens (CD19 for B-cell ALL/DLBCL; BCMA for myeloma). Commercial products available in India and UAE include tisagenlecleucel (Kymriah®) and axicabtagene ciloleucel (Yescarta®). CAR-T therapy has achieved CR rates of 70–90% in heavily pre-treated B-ALL and is increasingly used before or instead of allo-HSCT in certain indications. Requires a 28-day manufacturing window.

• Mesenchymal Stem Cell (MSC) Therapy: Expanded MSCs derived from bone marrow, adipose tissue, or umbilical cord Wharton's Jelly are used for steroid-refractory acute GvHD (Grade III–IV), Crohn's disease fistulae (darvadstrocel/Alofisel® protocol), and as adjunctive immunomodulatory therapy.

• Donor Lymphocyte Infusion (DLI): Infusion of additional donor lymphocytes post-allogeneic HSCT to boost GvT effect in cases of relapse or poor engraftment.

SUPPORTIVE TECHNOLOGY PLATFORMS:

• HEPA-filtered positive-pressure isolation rooms (Class 10,000 clean rooms)

• Real-time chimerism monitoring by STR-PCR (short tandem repeat polymerase chain reaction) to track engraftment and detect relapse

• MRD (Minimal Residual Disease) monitoring by multiparametric flow cytometry or NGS-MRD panels

• Prophylactic antifungal (micafungin or voriconazole), antiviral (acyclovir, prophylactic letermovir for CMV), and antibacterial (fluoroquinolone) regimens during aplasia

• GCSF-stimulated peripheral blood preferred over traditional bone marrow harvest in most adult protocols (faster neutrophil and platelet engraftment)

PHASE 1 — REMOTE PRE-TRANSPLANT EVALUATION (4–8 weeks before travel):

• GAF Healthcare coordinates remote consultation with the transplant physician; patient submits all prior medical records, pathology slides, bone marrow biopsy reports, and imaging digitally.

• HLA typing initiated at a local laboratory using a GAF-approved test kit or at the destination centre.

• Disease restaging imaging (PET-CT or CT-CAP) performed locally and reviewed remotely.

• Fitness assessment: ECHO, PFTs, LFTs, RFTs, infectious serology.

• Donor search initiated simultaneously through international registries if no matched sibling is available.

• Travel and visa arrangements commenced (e-Medical visa for India: 5 business days processing; UAE medical visa with hospital invitation letter).

PHASE 2 — ARRIVAL AND IN-COUNTRY PRE-TRANSPLANT WORKUP (Days -21 to -7):

• Arrival at destination; GAF Healthcare airport transfer to partner hospital or pre-arranged hotel/serviced apartment.

• Admission to transplant unit; repeat bloodwork and confirmatory HLA typing at the centre's accredited laboratory.

• Hickman line or peripherally inserted central catheter (PICC) line placed by interventional radiology.

• Autologous patients: stem cell mobilisation with G-CSF ± plerixafor (Days -14 to -10); apheresis collection (1–3 sessions) once CD34+ cells peak in peripheral blood; cells cryopreserved in liquid nitrogen.

• Allogeneic patients: donor undergoes G-CSF mobilisation and apheresis at a coordinated collection centre; cells transported fresh (preferred for peripheral blood) or cryopreserved.

• Final consent, anaesthesia/cardiology clearance, and patient education sessions.

PHASE 3 — CONDITIONING REGIMEN (Days -7 to -1 or -2):

• Patient admitted to HEPA-filtered isolation room.

• Conditioning chemotherapy administered per protocol (e.g., BEAM over 6 days for lymphoma; BuCy IV over 4 days for leukaemia; high-dose melphalan over 2 days for myeloma).

• Prophylactic antiemetics, hydration, MESNA bladder protection (for cyclophosphamide), and mucositis prevention (cryotherapy, oral care protocols) initiated.

• Patient monitoring: daily CBC, LFTs, RFTs, weight, and mucositis grading (WHO scale).

PHASE 4 — STEM CELL INFUSION (Day 0):

• Cryopreserved cells thawed in a 37°C water bath and infused intravenously over 30–60 minutes under continuous nursing and physician supervision.

• Vital signs and DMSO (cryoprotectant) reactions monitored; pre-medication with hydrocortisone and chlorphenamine minimises infusion reactions.

• Day 0 is documented as the patient's "transplant birthday" — the reference point for all post-transplant milestones.

PHASE 5 — ENGRAFTMENT AND EARLY POST-TRANSPLANT PERIOD (Days +1 to +30):

• Patient remains in isolation during the aplastic nadir (ANC < 500/µL), typically Days +5 to +14.

• Daily monitoring for fever (neutropenic fever protocols: broad-spectrum IV antibiotics per IDSA guidelines), mucositis, electrolyte imbalances, and early GvHD signs (rash, diarrhoea, jaundice).

• Red cell and platelet transfusion support as required (irradiated, CMV-negative blood products).

• Neutrophil engraftment typically confirmed by Day +10 to +16 (autologous) or Day +14 to +21 (allogeneic).

• Platelet engraftment: Day +14 to +28.

• Discharge from hospital isolation to a monitored outpatient setting upon ANC > 500/µL, tolerating oral medications, afebrile, and adequate nutrition.

PHASE 6 — OUTPATIENT MONITORING IN-COUNTRY (Days +30 to +60 or longer):

• Patient stays in GAF Healthcare-arranged serviced accommodation near the transplant centre.

• Visits to transplant outpatient clinic 3× per week initially, reducing to weekly as counts stabilise.

• For allogeneic patients: chimerism testing (STR-PCR) at Day +30, +60, +100; tacrolimus/cyclosporine levels monitored and adjusted; MRD testing.

• CMV reactivation monitored weekly by CMV PCR; pre-emptive ganciclovir/valganciclovir if viral load rises.

• Immunisation plan discussed (live vaccines deferred ≥ 24 months post-allogeneic HSCT; killed vaccines restarted from Month 6).

• Letermovir CMV prophylaxis continued to Day +100 in CMV-seropositive allogeneic recipients.

PHASE 7 — FIT-TO-FLY CLEARANCE AND DEPARTURE (Weeks 6–12 post-transplant):

• Autologous recipients: fit-to-fly clearance typically at 6–8 weeks post-transplant if engraftment is complete, no active infection, and patient is tolerating oral medications independently.

• Allogeneic recipients: clearance typically at 8–12 weeks; requires stable counts, absence of acute GvHD grade ≥ II, no active infection, and haematology team approval.

• GAF Healthcare coordinates comprehensive discharge package: digital medical summary, long-term medication list, immunisation schedule, emergency contact protocols for home-country physicians, and 90-day remote follow-up consultations via telemedicine.

• Medical travel insurance verification and in-flight health guidance provided.