High-Dose Treatment and Haematopoietic Stem Cell Transplantation in Developing Countries

A Victorian medicine made from bone marrow.

The use of high-dose treatment (HDT) with autologous or allogeneic haematopoietic stem cell support was discussed at the Annual Meeting of the INCTR, focusing on the specific problems surrounding the use of both treatment modalities in the developing country setting. Ama Rohatiner (St. Bartholomew's Hospital, London) and Aziza Shad (Georgetown University, Washington DC) introduced the subject as treatment for adults and children respectively.

The terminology can be confusing; the differences between the two treatment approaches are critical, relating not only to the source of stem cells, but also reflecting differences in the indications for each type of treatment, training needs of medical and nursing staff, facilities required and, not least, the cost.

HDT refers to the use of gram doses of chemotherapy, supported by autologous peripheral blood progenitor cells (PBPC), bone marrow suppression being the dose limiting toxicity. In contrast, haematopoietic stem cell transplantation involves the use of a myeloablative (or non-myeloablative) conditioning regimen, followed by infusion of bone marrow or PBPC from an HLA identical sibling donor (or HLA identical, unrelated or 'volunteer' donor). An allograft can be regarded as the ultimate form of immunotherapy, relying as much on the immunologically mediated 'graft-versus-tumour' effect as on the efficacy of the myeloablative regimen.

HDT + autologous haematopoietic stem cell support

A treatment modality used predominantly in adults, this is now regarded as 'standard of care' in some countries for younger, newly diagnosed patients in second complete (or partial) remission of diffuse large B-cell lymphoma, selected patients with recurrent Hodgkin Lymphoma and younger newly diagnosed patients with myeloma, following initial combination chemotherapy. Its role in other haematological malignancies remains experimental.

The use of PBPC has replaced autologous bone marrow, blood count recovery being significantly faster, making the treatment safer and cheaper. Whilst specific expertise (and equipment) are required to enable PBPC to be collected and cryopreserved, departments experienced in the management of patients with acute leukaemia should be well able to look after such patients.

Allografting

Allogeneic bone marrow transplantation should only carried out at specialised centres. The indications are: consolidation of first remission in 'high-risk' AML, consolidation of 2nd remission of AML and ALL and as treatment for younger patients with chronic myeloid leukaemia and aplastic anaemia. The problems occur in the post-transplant period, the so-called 'first 100 days', relating to the management of acute graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infection and subsequently, complications of chronic GVHD. One of the difficulties in the developing country setting is the need for close follow-up afterwards, some centres admitting patients for the entire 3 months with obvious implications for cost (both financial and 'human').

Professor Zeba Aziz (Jinnah Hospital, Lahore) supported the development of HDT, as therapy for selected younger patients with lymphoma. She stressed the importance of being realistic with regard to selection of patients for whom such treatment would be given with curative intent. Dr. Suresh Advani (Jaslock Hospital, Mumbai) agreed and went on to discuss the importance of having referral centres for children and young adults with acute leukaemia for whom an allograft would be the only curative therapy when conventional chemotherapy had failed. Dr. Mahmoud Al-Jurf (King Faisal Hospital and Research Centre, Riyadh) pointed out that whilst in the West only 1 in 4 patients would be expected to have an HLA identical sibling donor, in developing countries the chances are higher, since families are generally larger. He focussed on the use of allografting for severe aplastic anaemia and CML, alluding to the special issues of performing allografts in the Middle East, namely, the high incidence of seropositivity for CMV and Hepatitis B infection, also noting the incidence of TB in endemic areas. Dr. Hossam Kamel (NCI, Cairo) described the situation in Egypt as a model for the development of allografting in a resource-poor country, but alluded to the difficulties of trying to reconcile 'what is possible' with 'what is available'. He described the specific problems of allografting in Egypt where there is high incidence of Hepatitis B and C infection and the endemic problem of schistosomiasis, which can result in 'silent' peripheral fibrosis of the liver and subsequent fatal veno-occlusive disease.

The discussion centred on the justification for and logistics of developing expensive treatments applicable to few patients, as compared to measures for the prevention and early diagnosis of common cancers. The latter public health priorities are hard to reconcile with what are perceived to be the competing needs of relatively small numbers of patients who nonetheless have potentially curable illnesses. It is now possible to define who should (and who should not) have HDT or an allograft and, in the developing country setting the question of selection of patients is crucial.

Although no formal consensus was sought, there appeared to be agreement that where well trained staff and the necessary infrastructure are in place, HDT or allografts should be offered to appropriate candidates who fulfill predetermined criteria for patient selection. However, careful consideration would need to be given to the priority of such programs in the overall context of cancer control, or in the programs of individual institutions, particularly if publicly funded. Ideally, service provision should be on a regional basis to avoid unnecessary duplication.

Ama Rohatiner, Director of INCTR UK Office.