Leukemia Treatment in India and UAE | Complete Patient Guide

• ELIGIBILITY — GENERAL: Adults and paediatric patients with a confirmed haematological malignancy diagnosis (bone marrow biopsy, flow cytometry, cytogenetics, and molecular profiling are mandatory prerequisites before any treatment consultation)

• ACUTE LEUKAEMIA (ALL/AML): Newly diagnosed patients with ECOG performance status 0–2; patients with relapsed/refractory disease being evaluated for salvage therapy or transplant; patients who have failed 1–2 lines of prior therapy elsewhere seeking second-opinion protocol optimisation

• CML: Patients in chronic phase intolerant or resistant to first- or second-generation TKIs; patients in accelerated or blast phase being considered for third-generation TKI (ponatinib, asciminib) bridging to allo-HSCT

• CLL: Patients with del(17p) or TP53 mutation requiring BTK inhibitor (ibrutinib, acalabrutinib) or venetoclax-based therapy; Richter transformation requiring aggressive chemoimmunotherapy evaluation

• BMT CANDIDATES: Patients with HLA-matched sibling donor or 8/10 to 10/10 matched unrelated donor identified; patients in morphological CR1 or CR2 with MRD negativity preferred; adequate end-organ function (creatinine clearance >50 mL/min, LVEF >45% on ECHO, bilirubin <2× ULN, DLCO >50% on PFTs)

• REQUIRED DIAGNOSTIC WORKUP PRIOR TO ARRIVAL:

• Bone marrow biopsy with trephine (recent, within 4 weeks)

• Peripheral blood flow cytometry immunophenotyping

• Conventional karyotyping (G-banding) and FISH panel (BCR-ABL1, MLL, FLT3, NPM1, TP53, del17p, del13q)

• Next-Generation Sequencing (NGS) 28- to 54-gene haematological malignancy panel

• MRD assessment (PCR or multiparameter flow cytometry)

• PET-CT scan (for ALL with extramedullary disease, or CLL with Richter transformation)

• CT chest/abdomen/pelvis with contrast

• Cardiac evaluation: 12-lead ECG + 2D Echocardiogram (LVEF assessment mandatory pre-BMT)

• Pulmonary Function Tests (spirometry + DLCO, mandatory pre-BMT conditioning)

• LFTs, RFTs, viral serology (HBsAg, Anti-HCV, HIV, CMV IgG, EBV IgG)

• HLA typing (patient and potential donors) if BMT is contemplated

• CONTRAINDICATIONS (RELATIVE AND ABSOLUTE):

• ECOG performance status ≥3 (relative; may preclude intensive chemotherapy or BMT conditioning)

• Severe uncontrolled cardiac dysfunction (LVEF <35%)

• Refractory active systemic infection at time of planned treatment

• Active hepatitis B (must be treated/suppressed prior to immunosuppression)

• No suitable HLA-matched donor identified (for allo-HSCT; may redirect to haploidentical or cord blood transplant evaluation)

• Uncontrolled psychiatric illness precluding informed consent and compliance with long-term immunosuppression

CHEMOTHERAPY PROTOCOLS Induction chemotherapy is the backbone of acute leukaemia management. For AML, the '7+3' regimen (cytarabine 100–200 mg/m² continuous infusion × 7 days + daunorubicin or idarubicin × 3 days) remains the standard induction platform, with CPX-351 (liposomal cytarabine/daunorubicin) now preferred for therapy-related AML or AML with myelodysplasia-related changes. For ALL, risk-stratified regimens such as hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) or BFM-based protocols are employed. Ph+ ALL mandates concurrent TKI therapy (dasatinib or ponatinib) with chemotherapy. CNS prophylaxis via intrathecal methotrexate ± cytarabine is standard for ALL. Consolidation with high-dose cytarabine (HiDAC, 3 g/m² q12h × 6 doses) constitutes post-remission therapy for favourable-risk AML. CLL is treated with chemoimmunotherapy (FCR: fludarabine, cyclophosphamide, rituximab) in fit, IGHV-mutated, del(17p)-negative patients, or with novel agents as primary therapy in high-risk biology.

TARGETED MOLECULAR THERAPY Targeted therapies have transformed leukaemia management across all subtypes: • CML: First-line TKIs — imatinib (generic, cost-effective), dasatinib, nilotinib; Second-line (resistance/intolerance): bosutinib, ponatinib; Third-line/T315I mutation: asciminib (STAMP inhibitor). BCR-ABL1 molecular monitoring by qPCR every 3 months guides response assessment (EMR, MMR, MR4, MR4.5). • FLT3-mutated AML: Midostaurin (FDA-approved in combination with '7+3') for newly diagnosed; gilteritinib for relapsed/refractory FLT3-ITD or TKD-mutated AML. • IDH1/2-mutated AML: Ivosidenib (IDH1) and enasidenib (IDH2) — oral targeted agents causing differentiation of leukaemic blasts; increasingly used as monotherapy in older/unfit patients. • BCL-2 inhibition: Venetoclax in combination with azacitidine (Ven-Aza) is now the standard of care for AML patients unfit for intensive chemotherapy (CR/CRi rates of 66–70% in pivotal VIALE-A trial); also used in CLL (venetoclax + obinutuzumab, venetoclax + ibrutinib). • BTK inhibitors (CLL/MCL): Ibrutinib, acalabrutinib, zanubrutinib — covalent or non-covalent BTK inhibition; zanubrutinib and acalabrutinib have superior cardiac safety profiles vs. ibrutinib. • CD20-directed immunotherapy: Rituximab, obinutuzumab, ofatumumab — used in combination regimens for B-cell leukaemias. • CD19/CD3 Bispecific T-Cell Engager (BiTE): Blinatumomab — approved for MRD+ ALL and relapsed/refractory B-ALL; administered as continuous IV infusion requiring hospitalisation for cycle 1 due to CRS monitoring. • CAR-T Cell Therapy: Tisagenlecleucel (Kymriah) for paediatric/young adult relapsed/refractory ALL; axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel for certain B-cell malignancies. Available at select CAR-T centres in India (Tata Memorial Mumbai, AIIMS Delhi, Apollo) and the UAE (Cleveland Clinic Abu Dhabi, Burjeel Medical City Abu Dhabi). Requires leukapheresis, 3–4 week manufacturing, and specialised CRS management infrastructure (ICU-capable units, tocilizumab on standby).

BONE MARROW TRANSPLANTATION (HSCT) HSCT is the definitive curative treatment for eligible leukaemia patients: • Autologous HSCT (Auto-SCT): Patient's own stem cells harvested during remission; used primarily in selected ALL cases (not standard for AML); lower transplant-related mortality (TRM) but higher relapse risk. • Allogeneic HSCT (Allo-SCT): Donor stem cells from matched sibling donor (MSD), matched unrelated donor (MUD, 8–10/10 HLA matching via international registries), haploidentical donor (parent/child/sibling, 50% HLA match using post-transplant cyclophosphamide/PTCy-based GVHD prophylaxis), or umbilical cord blood. • Myeloablative Conditioning (MAC): Busulfan/cyclophosphamide (Bu-Cy) or TBI-based conditioning for younger, fit patients (age <50–55); maximises graft-versus-leukaemia (GVL) effect. • Reduced-Intensity Conditioning (RIC): Fludarabine-based regimens for older patients (age >55–65) or those with comorbidities; lower TRM but requires robust GVL effect for disease control. • GVHD Prophylaxis: Standard — calcineurin inhibitor (tacrolimus/cyclosporine) + methotrexate or MMF; novel — post-transplant cyclophosphamide (PTCy) now widely used for haploidentical and MUD transplants to reduce severe GVHD without compromising GVL. • Graft-versus-Host Disease (GVHD) Management: Acute GVHD (Grades II–IV) managed with systemic corticosteroids; steroid-refractory acute GVHD with ruxolitinib (JAK1/2 inhibitor, FDA-approved) or extracorporeal photopheresis (ECP). Chronic GVHD managed with ibrutinib, ruxolitinib, or belumosudil. • MRD Monitoring Post-Transplant: Serial MRD assessment by qPCR or NGS at D+30, D+60, D+90, D+180 guides decisions on immunosuppression tapering and donor lymphocyte infusion (DLI) for impending relapse.

RADIATION THERAPY (ADJUNCTIVE) Cranial or craniospinal irradiation (12–24 Gy) for CNS-positive ALL or CNS prophylaxis in high-risk cases. Total Body Irradiation (TBI, 12 Gy in 6 fractions) as component of myeloablative conditioning pre-BMT at equipped centres. Modern centres use IMRT and VMAT-based techniques to minimise neurotoxicity and cataract risk.

PHASE 1 — PRE-ARRIVAL PREPARATION (2–4 WEEKS BEFORE TRAVEL) Step 1: GAF Healthcare receives all available medical records (bone marrow biopsy pathology, cytogenetics/NGS report, imaging, prior treatment history). A senior haematologist/oncologist at the partner centre reviews the case and issues a detailed second-opinion report with recommended treatment protocol, estimated duration, and cost estimate within 48–72 hours. Step 2: Patient and family complete the visa application. Indian e-Medical Visa is applied online (typically approved within 3–5 business days). For UAE, most nationalities receive visa-on-arrival or 30-day tourist visa, with medical visit facilitation through the hospital's international patient services office. Step 3: GAF Healthcare coordinator confirms hospital admission date, pre-admission lab requisition (if any tests need to be repeated), and arranges airport pickup and accommodation near the treatment centre for the patient's attendant(s).

PHASE 2 — ADMISSION & BASELINE ASSESSMENT (DAYS 1–5) Step 4: On arrival, the patient is admitted to the haematology/bone marrow transplant unit. A comprehensive baseline workup is completed or verified: CBC with differential, bone marrow biopsy (if not done within 4 weeks), flow cytometry, repeat cytogenetics if required, cardiac ECHO, PFTs, CT/PET-CT, full metabolic panel, and infectious disease serology. Step 5: Multidisciplinary Tumour Board (MDT) review — haematologist, transplant physician, transfusion medicine specialist, infectious disease specialist, clinical pharmacist, and dietitian — finalise the treatment plan and obtain informed consent. Step 6: A central venous catheter (PICC line or Hickman/Broviac tunnelled catheter) is placed under ultrasound guidance to facilitate chemotherapy administration, blood sampling, and supportive transfusions.

PHASE 3 — TREATMENT DELIVERY For Chemotherapy (Induction): Step 7 (Days 1–7/10): Induction chemotherapy begins (e.g., '7+3' for AML; hyper-CVAD cycle 1A for ALL). Daily CBC, renal and hepatic function, electrolytes, and uric acid monitoring. Allopurinol or rasburicase prophylaxis for tumour lysis syndrome (TLS). G-CSF administered post-nadir to support neutrophil recovery. Intrathecal chemotherapy administered on designated days for ALL. Step 8 (Days 10–21): Nadir period — patient is neutropaenic and hospitalised in a HEPA-filtered, positive-pressure single room. Prophylactic antifungal (posaconazole/voriconazole), antiviral (acyclovir), and antibacterial (levofloxacin) therapy. Platelet and red cell transfusion support as required. G-CSF continues until ANC >1.0 × 10⁹/L. Step 9 (Days 21–28): Bone marrow assessment (D+28 or D+35 depending on protocol) to assess morphological remission. MRD testing by PCR or multiparameter flow cytometry. MDT review of response and decision regarding consolidation or transplant pathway.

For BMT (following induction remission — typically Month 2–4): Step 10 (Weeks 1–2 of BMT Phase): Donor work-up completed (related or unrelated donor). Mobilisation and collection of peripheral blood stem cells (G-CSF-mobilised PBSC) or bone marrow harvest under general anaesthesia from donor. Cryopreservation of graft at the transplant centre's cell therapy laboratory. Step 11 (Days −7 to −1, Conditioning): Myeloablative (Bu-Cy or TBI-based) or Reduced-Intensity Conditioning (Flu-Bu2 or Flu-Mel) administered. Patient is in strict isolation in a bone marrow transplant unit (BMT room with HEPA filtration, positive pressure, visitor restriction protocols). Step 12 (Day 0, Transplant Day): Thawed or fresh stem cell graft infused via central venous catheter over 1–4 hours. The patient may experience mild rigors, nausea, or haemodynamic fluctuation; continuous monitoring for 4–6 hours post-infusion. Step 13 (Days +1 to +30, Engraftment Phase): Severe aplasia phase — daily CBC, electrolytes, renal function, CMV/EBV surveillance by PCR twice weekly. GVHD prophylaxis (tacrolimus + methotrexate or PTCy). Engraftment typically expected at Day +14 to +21 for PBSC (ANC >0.5 × 10⁹/L on 3 consecutive days). First bone marrow assessment and chimerism testing at Day +28–30.

For Targeted Therapy (CML/FLT3/IDH/BCL-2 inhibitors): Step 14 (Days 1–7): TKI or targeted agent initiated. Baseline molecular response assessment. Dose titration and toxicity monitoring (QTc prolongation for nilotinib, pleural effusion for dasatinib, differentiation syndrome for IDH inhibitors, tumour flare/TLS for venetoclax). Structured venetoclax ramp-up (20–100–200–400 mg over 5 weeks) performed in hospital/day-unit setting with TLS monitoring.

PHASE 4 — EARLY RECOVERY & DISCHARGE PLANNING (POST-INDUCTION: WEEK 4–6; POST-BMT: WEEKS 6–16) Step 15: Following induction chemotherapy, patients achieving remission with haematological recovery (ANC >1.0, Plt >50) are discharged to outpatient/residential care near the hospital for consolidation cycle planning. GAF Healthcare arranges serviced accommodation for patient and 1–2 attendants within 2–5 km of the treating hospital. Step 16 (Post-BMT, Days +30 to +100): Weekly outpatient clinic visits for CBC, metabolic panel, tacrolimus/cyclosporine levels, CMV/EBV monitoring, and GVHD assessment. Patients must reside within 30–60 minutes of the transplant centre. Intravenous antimicrobial infusions, IVIG supplementation, and transfusion support are administered in the day-care unit. Step 17 (Day +100 Assessment): Comprehensive disease response evaluation — bone marrow biopsy, full chimerism analysis, MRD testing, and organ function review. MDT decision regarding immunosuppression tapering, Donor Lymphocyte Infusion (DLI) for mixed chimerism, or maintenance therapy.

PHASE 5 — FIT-TO-FLY CLEARANCE & REMOTE FOLLOW-UP Step 18: Fit-to-fly assessment conducted by the treating haematologist. International travel is cleared when: (Chemotherapy patients) ANC >1.0 × 10⁹/L, Plt >50, no active infection, patient clinically stable — typically 4–6 weeks post-induction. (BMT patients) Minimum 90 days post-transplant, full engraftment confirmed, no active acute GVHD, no active infection, and the patient has been coached on GVHD recognition and immunosuppression adherence. Step 19: GAF Healthcare provides a comprehensive medical discharge summary, current medication list with generic equivalents, emergency contact protocol, and instructions for the receiving haematologist in the home country for seamless continuity of care.