Bone Marrow Transplant in India and UAE | Complete Patient Guide

ELIGIBLE DIAGNOSES & INDICATIONS:

• Acute Myeloid Leukaemia (AML): intermediate- or adverse-risk cytogenetics (e.g., monosomy 7, complex karyotype, FLT3-ITD without NPM1), or relapsed/refractory disease in CR1 or CR2

• Acute Lymphoblastic Leukaemia (ALL): Philadelphia chromosome-positive ALL, MRD-positive after induction, or high-risk features (e.g., hypodiploidy, KMT2A rearrangement)

• Myelodysplastic Syndrome (MDS): IPSS-R score intermediate or above, or therapy-related MDS

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

• Multiple Myeloma: autologous HSCT post-induction (bortezomib/lenalidomide/dexamethasone or daratumumab-based regimens) as standard consolidation for transplant-eligible patients under 70

• Non-Hodgkin Lymphoma: relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma sensitive to salvage chemotherapy (autologous HSCT); or allogeneic for chemorefractory disease

• Hodgkin Lymphoma: relapsed/refractory disease after second-line therapy, PET-negative before transplant

• Aplastic Anaemia: severe or very severe (SAA/vSAA) failing immunosuppression, or upfront allogeneic HSCT in patients under 40 with matched sibling donors

• Haemoglobinopathies: sickle cell disease (Glucksberg Class I–II) and transfusion-dependent thalassaemia major in paediatric and young adult patients

• Primary Immunodeficiencies: SCID, Wiskott-Aldrich syndrome, chronic granulomatous disease

REQUIRED PRE-TRANSPLANT DIAGNOSTICS:

• Bone marrow biopsy with cytogenetics (conventional karyotype + FISH panel), flow cytometry immunophenotyping, and MRD quantification (NGS-MRD preferred)

• HLA typing (patient and all potential donors) at high-resolution allele level: HLA-A, -B, -C, -DRB1, -DQB1

• PET-CT scan (for lymphoma patients to confirm chemosensitivity before conditioning)

• Cardiac evaluation: 2D echocardiography (LVEF must be ≥ 45–50%), ECG, and NT-proBNP if cardiotoxic prior therapy used

• Pulmonary Function Tests (PFTs): DLCO must be ≥ 50% predicted; CT chest to exclude occult fungal or bacterial infection

• Renal function (GFR ≥ 50 mL/min preferred for full myeloablative conditioning)

• Liver function, hepatitis B/C serology, HIV, CMV, EBV, HSV, VZV, Toxoplasma IgG serostatus

• Dental evaluation and caries clearance before conditioning

• Fertility counselling and cryopreservation discussion (sperm/oocyte banking) prior to gonadotoxic conditioning

• Psychosocial assessment and nutritional status (BMI, albumin, pre-transplant functional status using Karnofsky/Lansky score)

CONTRAINDICATIONS:

• LVEF < 40% or uncontrolled heart failure

• DLCO < 40% predicted or active pulmonary infection

• Uncontrolled active infection (bacterial, fungal, or viral) at time of planned conditioning

• Severe hepatic dysfunction (Child-Pugh C cirrhosis or bilirubin > 2× ULN unless disease-related)

• Active, uncontrolled malignancy not responsive to salvage therapy (chemorefractory disease is a relative contraindication for allogeneic HSCT; must demonstrate at least partial response)

• Karnofsky Performance Status < 60% (relative contraindication; RIC regimens may allow PS 50–60%)

• Significant, uncontrolled psychiatric illness that would preclude adherence to strict isolation and complex medication regimens

• Age > 70 years for myeloablative conditioning (RIC regimens extend eligibility to age 75 in select patients with excellent organ function)

AUTOLOGOUS HAEMATOPOIETIC STEM CELL TRANSPLANTATION (Auto-HSCT):

The patient's own peripheral blood stem cells (PBSCs) are mobilised using G-CSF (filgrastim or plerixafor-augmented mobilisation for poor mobilisers), collected by leukapheresis, cryopreserved in liquid nitrogen, and re-infused after high-dose conditioning chemotherapy. Standard conditioning regimens include BEAM (carmustine, etoposide, cytarabine, melphalan) for lymphomas and high-dose melphalan (200 mg/m²) for multiple myeloma. Tandem autologous transplantation is considered for high-risk myeloma (ISS Stage III, high-risk cytogenetics such as del(17p), t(4;14), gain(1q)). Because the patient's own cells are reinfused, there is no GvH disease risk, but also no GvL effect; relapse risk depends entirely on disease biology and consolidation/maintenance therapy (e.g., lenalidomide maintenance post-auto in myeloma, per IFM 2005-02 and CALGB 100104 trial data).

ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION (Allo-HSCT) — MATCHED SIBLING DONOR (MSD):

Considered the gold standard for allogeneic transplantation. A 10/10 HLA-matched sibling provides the lowest GvHD risk and best GvL effect. Conditioning is either myeloablative (BuCy: busulfan IV 3.2 mg/kg/day × 4 days + cyclophosphamide; or TBI 12 Gy fractionated + cyclophosphamide) or reduced-intensity (Flu/Bu2: fludarabine + 2-day busulfan, appropriate for patients over 50 or with organ comorbidities). GvHD prophylaxis: calcineurin inhibitor (tacrolimus or cyclosporine) + methotrexate (short-course) or mycophenolate mofetil (MMF).

ALLOGENEIC HSCT — MATCHED UNRELATED DONOR (MUD) VIA BONE MARROW REGISTRY:

When no matched sibling is available, high-resolution HLA-matched unrelated donors are sourced from international registries (NMDP/Be The Match, DKMS, DATRI in India). A 10/10 MUD match carries GvHD risk intermediate between MSD and haploidentical. Post-transplant cyclophosphamide (PTCy: 50 mg/kg on days +3 and +4) is increasingly used as GvHD prophylaxis in the MUD setting, replacing or augmenting conventional CNI-based approaches.

HAPLOIDENTICAL TRANSPLANTATION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE (Haplo-PTCy):

A transformative advance pioneered at Johns Hopkins and validated globally, Haplo-PTCy uses a 50% HLA-matched first-degree relative (parent, child, or sibling) as the donor. Because virtually every patient has at least one haploidentical relative, the donor search phase is eliminated, reducing time-to-transplant significantly — critical in aggressive leukaemias. PTCy selectively eliminates alloreactive T-cells proliferating early post-infusion while sparing regulatory and memory T-cells, resulting in GvHD rates comparable to MUD transplants. Major transplant centres in India and the UAE now report Haplo-PTCy outcomes — including non-relapse mortality, 2-year overall survival, and GvHD-free relapse-free survival (GRFS) — equivalent to matched donor transplants for AML in CR1.

UMBILICAL CORD BLOOD TRANSPLANTATION (UCBT):

Used when no matched adult donor is available and time is critical, or in paediatric patients. Double cord blood units are used in adults to provide sufficient cell dose. Engraftment is slower (day +21 to +35) and the risk of graft failure is higher, but the lower HLA-match requirement and the immunological naivety of cord-derived T-cells reduce chronic GvHD rates. Select centres in India (particularly in major metropolitan cities) and the UAE maintain cord blood bank partnerships.

BONE MARROW HARVEST (Surgical) vs. PERIPHERAL BLOOD STEM CELL (PBSC) COLLECTION:

Stem cells for allogeneic transplant are collected either by surgical bone marrow harvest under general anaesthesia (600–1000 mL aspirated from posterior iliac crests) or by G-CSF-mobilised leukapheresis of peripheral blood. PBSC grafts engraft faster and are used most commonly; marrow grafts may be preferred in aplastic anaemia and haemopoietic syndromes where lower T-cell content reduces chronic GvHD risk, per IBMTR data.

CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY (CAR-T) AS AN ALTERNATIVE OR BRIDGE:

For relapsed/refractory B-cell ALL and large B-cell lymphoma, CAR-T therapy (tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel) represents an emerging alternative or bridge strategy before allo-HSCT consolidation. Select advanced oncology centres in India and the UAE now offer commercially approved CAR-T programmes or clinical trial access. GAF Healthcare can facilitate evaluation for CAR-T eligibility in conjunction with or as a preceding step to BMT planning.

GRAFT-VERSUS-HOST DISEASE (GvHD) PROPHYLAXIS & TREATMENT TECHNOLOGIES:

• Acute GvHD prophylaxis: PTCy-based platforms, calcineurin inhibitors (tacrolimus with target trough 5–15 ng/mL), MMF, anti-thymocyte globulin (ATG: rabbit ATG or equine ATG)

• Chronic GvHD management: ruxolitinib (JAK1/2 inhibitor, FDA-approved second-line), ibrutinib (BTK inhibitor), belumosudil (ROCK2 inhibitor), extracorporeal photopheresis (ECP)

• CD34+ graft manipulation / T-cell depletion using CliniMACS Prodigy platform for high-risk GvHD scenarios (available at select centres)

• Bone Marrow Transplantation Units at top Indian and UAE centres are equipped with ISO Class 5 HEPA-filtered positive-pressure isolation rooms, real-time chimerism monitoring by STR-PCR, and MRD surveillance by flow cytometry and ddPCR at standardised post-transplant intervals (day +30, +100, +180, +365)

PHASE 1 — REMOTE PRE-EVALUATION (Weeks 1–4, from home country): Patient submits complete medical records to GAF Healthcare's clinical team, including bone marrow biopsy reports, cytogenetics, flow cytometry, PET-CT scans, echocardiogram, PFTs, and prior treatment history. GAF Healthcare's partnered transplant physician reviews records and provides a detailed second opinion, transplant feasibility assessment, proposed conditioning regimen, and donor strategy recommendation within 5–7 business days. Visa and travel logistics planning commences in parallel.

PHASE 2 — ARRIVAL & PRE-TRANSPLANT WORKUP (Days −30 to −10 before conditioning): Patient arrives in India or the UAE and is admitted or seen in outpatient transplant clinic. Comprehensive repeat baseline investigations are performed: repeat bone marrow biopsy and MRD quantification to confirm remission status, updated PFTs, ECHO, ECG, renal and liver function panel, infectious disease serology (CMV, EBV, HSV, hepatitis B/C, HIV, Toxoplasma), and dental clearance. High-resolution HLA typing is confirmed for patient and donor. A central venous catheter (Hickman line or PICC) is placed under ultrasound guidance for conditioning drug delivery, stem cell infusion, and intensive monitoring. Donor undergoes G-CSF mobilisation (if PBSC collection planned) starting 5 days before scheduled infusion, or is admitted for surgical bone marrow harvest.

PHASE 3 — CONDITIONING REGIMEN (Days −7 to −1): High-dose or reduced-intensity conditioning chemotherapy (and/or total body irradiation if TBI-based regimen) is administered in the sterile transplant unit. The patient is monitored continuously for mucositis (managed with IV morphine PCA, sucralfate, and cryotherapy), nausea (ondansetron, dexamethasone, aprepitant), haemorrhagic cystitis (MESNA uroprotection, aggressive IV hydration with busulfan/cyclophosphamide regimens), and infectious prophylaxis is initiated: fluconazole or posaconazole, aciclovir, co-trimoxazole (PCP prophylaxis deferred until engraftment).

PHASE 4 — STEM CELL INFUSION (Day 0): Cryopreserved autologous cells are thawed and infused at bedside (auto-HSCT), or freshly collected donor PBSCs or marrow are infused via the central line (allo-HSCT). The infusion is administered over 1–4 hours under continuous cardiac and vital sign monitoring. Patients may experience DMSO-related flushing, nausea, or bradycardia during cryopreserved cell infusion, managed with antihistamines, antiemetics, and IV fluids.

PHASE 5 — ENGRAFTMENT PHASE & STERILE ISOLATION (Days +1 to +30): The most critical and medically intensive phase. Patient remains in HEPA-filtered positive-pressure isolation room. Prophylactic antibiotics (fluoroquinolones), antifungals, and antivirals are continued. Transfusion support with irradiated, leukodepleted packed red blood cells (haemoglobin threshold 80 g/L) and platelets (threshold 10 × 10⁹/L, or 20 × 10⁹/L if febrile) is provided. Febrile neutropenia episodes are managed with broad-spectrum IV antibiotics (piperacillin-tazobactam or meropenem for resistant organisms) and antifungal escalation (caspofungin or liposomal amphotericin B if fluconazole-resistant suspected). Engraftment is confirmed when ANC > 0.5 × 10⁹/L on three consecutive days — typically by day +14 to +21 for PBSC grafts and day +18 to +28 for marrow grafts. Weekly chimerism testing (STR-PCR) from day +30 confirms donor engraftment percentage.

PHASE 6 — EARLY POST-ENGRAFTMENT & GvHD MONITORING (Days +30 to +100): Patient transitions to outpatient transplant clinic (within the country, near the transplant centre) for twice-weekly to weekly review. GvHD prophylaxis medications (tacrolimus/cyclosporine + MMF or PTCy-based regimen) are continued and slowly tapered per protocol. Acute GvHD affecting skin (maculopapular rash), gut (diarrhoea > 500 mL/day), or liver (rising bilirubin) is staged by MAGIC criteria and treated with systemic corticosteroids (methylprednisolone 1–2 mg/kg/day) with rapid escalation to ruxolitinib or ECP for steroid-refractory cases. CMV and EBV reactivation are monitored by weekly quantitative PCR; pre-emptive therapy with valganciclovir or ganciclovir is initiated at defined viral load thresholds. MRD assessment is repeated at day +100. Patients must remain in-country and within accessible distance of the transplant centre throughout this phase.

PHASE 7 — FIT-TO-FLY ASSESSMENT (Weeks 10–16 post-infusion): Before international travel is approved, the transplant physician must confirm: (1) stable, full donor engraftment on chimerism testing; (2) no active acute GvHD above Grade I; (3) ANC consistently > 1.0 × 10⁹/L without G-CSF support; (4) transition to oral immunosuppression only, with stable tacrolimus or cyclosporine levels; (5) no active viral reactivation; (6) no recent transfusion dependence; (7) patient and accompanying caregiver are educated on emergency protocols and have confirmed follow-up with a haematologist in the home country. GAF Healthcare coordinates the medical summary, discharge letter, full medication list, and emergency contact details for the receiving haematologist.

PHASE 8 — LONG-TERM REMOTE FOLLOW-UP (Months 6–24+): Follow-up visits (which may include return trips to the transplant centre at months 6 and 12 for MRD assessment, chimerism testing, and chronic GvHD evaluation) are coordinated by GAF Healthcare's case management team. Immunisation schedule (live vaccines contraindicated until 24 months post-transplant and off immunosuppression) and vaccination re-priming (diphtheria, tetanus, pertussis, inactivated polio, hepatitis B, pneumococcal, influenza) is planned per EBMT/IDSA guidelines for post-transplant immune reconstitution.