Aplastic Anaemia BMT, IST & Advanced Care Access

Aplastic anaemia is a bone marrow failure disorder in which the bone marrow stops producing enough blood cells due to destruction of haematopoietic stem cells, usually by the patient's own immune system. The bone marrow is empty or very sparsely cellular. It is fundamentally different from leukaemia: in leukaemia, the marrow is overactive and filled with malignant (cancerous) cells; in aplastic anaemia, the marrow is depleted and the problem is too few cells, not malignant ones. Aplastic anaemia is treated with bone marrow transplantation or immune suppression, not chemotherapy aimed at killing cancer cells.

Aplastic anaemia is classified by severity based on blood count criteria (the Camitta criteria). Severe aplastic anaemia (SAA) requires a hypocellular bone marrow plus at least two of: neutrophils <0.5 × 10⁹/L, platelets <20 × 10⁹/L, or reticulocytes <20 × 10⁹/L. Very severe AA (vSAA) additionally requires neutrophils <0.2 × 10⁹/L. Non-severe AA does not meet these thresholds. Severity grade drives treatment urgency and choice — SAA/vSAA requires prompt definitive treatment (BMT or IST), while non-severe transfusion-independent AA may be observed. The distinction is critical because SAA/vSAA carries high mortality without treatment.

The answer depends on patient age, disease severity, and donor availability. For young patients (generally under 40) with severe or very severe AA who have a matched sibling donor, allogeneic bone marrow transplantation (BMT) is the preferred first-line treatment — it is potentially curative with low relapse risk. For patients without a matched sibling donor, older patients, or those with significant comorbidities, immune suppressive therapy (IST) with horse ATG + ciclosporin + eltrombopag (the RACE regimen) is standard and achieves approximately 80% haematological response. This decision should be made at a specialist haematology centre with both BMT and IST experience.

Anti-thymocyte globulin (ATG) is an antibody preparation made by immunising horses (hATG, Atgam) or rabbits (rATG, Thymoglobulin) with human thymocytes, producing antibodies that deplete T lymphocytes responsible for destroying haematopoietic stem cells. In aplastic anaemia, head-to-head trials have clearly demonstrated that horse ATG produces substantially better haematological response rates and survival than rabbit ATG in the first-line IST setting. Rabbit ATG should not be substituted for horse ATG in the frontline AA setting. Horse ATG may have limited availability in some countries — CancerFax can assist with access coordination.

Fanconi anaemia (FA) is an inherited bone marrow failure syndrome with a DNA repair defect that makes affected patients extremely sensitive to alkylating agents and radiation — the agents used in standard BMT conditioning regimens. If a patient with unrecognised FA receives standard chemotherapy conditioning, it can cause severe and potentially fatal toxicity. FA patients require a specially designed attenuated conditioning regimen. The DEB or MMC chromosomal fragility test reliably identifies FA before treatment begins. All patients with newly diagnosed AA — especially children and young adults — should be tested for FA before any conditioning treatment is planned.

Paroxysmal nocturnal haemoglobinuria (PNH) clones are blood cells that have lost surface proteins (GPI-anchors) due to a somatic mutation in the PIGA gene, making them vulnerable to complement-mediated destruction. Small PNH clones are very common in acquired aplastic anaemia and actually indicate that the disease is immune-mediated — patients with PNH clones tend to respond better to IST. Large PNH clones (>10–50% of granulocytes) can cause haemolysis and thrombosis, requiring eculizumab or ravulizumab (complement inhibitors). PNH clone testing by flow cytometry should be part of every AA diagnostic workup.

A proportion of patients with aplastic anaemia treated with IST develop clonal evolution over time — most importantly to myelodysplastic syndrome (MDS) or, rarely, to acute myeloid leukaemia (AML). The most concerning cytogenetic change is monosomy 7, which is associated with higher risk of MDS/AML evolution. For this reason, patients treated with IST should have regular bone marrow assessments with cytogenetics and molecular testing to detect early clonal changes. Patients who develop monosomy 7 or MDS features should be evaluated promptly for bone marrow transplantation before overt AML develops.

Yes — haploidentical bone marrow transplantation (using a half-matched parent, sibling, or child as donor, with post-transplant cyclophosphamide to prevent graft-versus-host disease) has become an important option for AA patients without a matched sibling or unrelated donor. Outcomes at experienced specialist centres have improved substantially with post-transplant cyclophosphamide-based protocols, and results are increasingly comparable to matched unrelated donor BMT. Several specialist BMT centres in India offer haploidentical HSCT for aplastic anaemia at internationally recognised quality standards.

Yes. CancerFax supports aplastic anaemia patients by reviewing bone marrow biopsy and blood count data to confirm severity grading, coordinating specialist haematology second opinions for BMT versus IST decision-making, helping identify the availability of horse ATG in different regions, facilitating referrals to accredited BMT centres in India for matched sibling, unrelated, and haploidentical transplants, and connecting patients to specialist programmes for inherited bone marrow failure (Fanconi anaemia, dyskeratosis congenita). Please share your medical reports through the CancerFax portal or contact our team to begin.