Developing a Haploidentical Transplant Program: An Indian Experience

Out of an estimated 20,000 patients requiring an allogeneic HCT in India, only 500 odd patients receive one. Keeping in cognisance the resource constraints, the major reason for the discordance lies in the lack of alternate donors. Whilst unrelated donor marrow and cord suffice for the ethnic majorities in Europe and the USA, such registries provide for less than 10% of HCT recipients due to both cost and an available match. With this background, we initiated a Haploidentical Family Donor HCT program in 2011.

In our initial screening of 50 patients referred for an allogeneic BMT, a matched family donor was available in 11 patients and a suitable Haploidentical family donor was available for 49, whereas a fully matched unrelated donor (10/10) was available for none. Hence we decided to develop a Haploidentical BMT program within the available resources. We chose a Posttransplant Cyclophosphamide (PTCY) based approach with PBSC as the graft source.

We have carried out 40 transplants in 32 patients over the last 3 years (AML-15; ALL-2; CML-BC-2; Lymphoma-2; Severe Aplastic Anemia (SAA)-10; Thalassemia-1). All received PBSC with PTCY on days 3 and 4 followed by cyclosporine and MMF. The conditioning regimen comprised of Fludarabine 150 mg/CY-30 mg/Melphalan-100 mg (SAA) or 120-140 mg (others) with Fludarabine and IV Busulfan (6.4-9.6 mg/kg) or Treosulfan 10-12 gm/m². 2GY TBI was offered to 4 patients instead of Melphalan.  Sirolimus was added later on day -7 pretransplant to the last 5 patients with SAA.

30/32 patients surviving beyond 21 days had successful engraftment with full donor chimerism, including 10/11 patients with SAA and Thalassemia. 6/8 evaluable patients undergoing a second Haploidentical HCT engrafted as well. Acute GVHD grade 2-4 developed in 3/32 patients. Day 100 NRM was 5/32 (15%) and the overall survival at 2 years was 55%. The major cause of NRM was infection with Carbapenem-resistant Gram Negative Bacilli accounting for 90% of the deaths. Chronic GVHD occurred in 10% of the evaluable patients. With stringent monitoring for CMV and preemptive therapy, only 1 patient succumbed to CMV disease. The outcome and cost of this extremely high risk group of patients was comparable to matched family donor BMT. PBSC as graft source was associated with a low incidence of both acute and chronic GVHD. We also studied the effect of Natural Killer Cell Ligand Mismatch (NKLMM) donor on the outcome in all our patients. NKLMM was associated with reduced incidence of relapse in patients with haematological malignancies (p=0.03). However, NKLMM donor was associated with poor outcome in patients with SAA (p=0.05).

In summary, Haploidentical HCT based on PTCY and PBSC graft is feasible and probably the most viable form of alternate donor HCT in resource constrained settings with outcomes comparable to matched donor HCT.