The PNH phenotype cells that emerge in most patients after CAMPATH-1H therapy are present prior to treatment

Paroxysmal nocturnal haemoglobinuria (PNH) cells are deficient in glycosylp hosphatidylinositol (GPT) linked antigens due to a somatic mutation of the PIG-A gene in a haemopoietic stem cell. II appears that a PNH clone reaches detectable proportions only when there is selection in its favour. GPI-def icient T lymphocytes have been identified in patients treated with CAMPATH- 1H, a monoclonal antibody against the GPI-linked CD52 molecule. CAMPATH-1H selects for cells that are deficient in CD52 (such as PNH-like cells) promo ting the development of a PNH-like clone (analogous to PNH). We report that 10/15 patients with chronic lymphocytic leukaemia developed PNH-like lymph ocytes after therapy with CAMPATH-1H. The remaining five patients developed no PNH-like cells at any stage, including one patient who received 12 week s of therapy. The inactivating PIG-A mutation has been identified in one pa tient. This mutation was detectable by an extremely sensitive mutation-spec ific PCR-based analysis in the patient's mononuclear cells prior to CAMPATH -1H therapy The frequency and phenotype of GPI-deficient lymphocytes after CAMPATH-1H and the detection of a PIG-A mutation in the lymphocytes prior t o CAMPATH-1H therapy indicated that such mutations were present in a very s mall proportion of cells prior to selection in their favour by CAMPATH-1H. This suggests that a large proportion of individuals have cells with PIG-A mutations that are not detectable by flow cytometry and thus may have the p otential to develop PNH.