Clinical characteristics predict response to antithymocyte globulin in paroxysmal nocturnal haemoglobinuria

Abstract

Seven patients with paroxysmal nocturnal haemoglobinuria (PNH) were treated with antithymocyte globulin (ATG). Each patient received ATG (20 mg/kg/d) for 8 d and prednisone to prevent or control serum sickness. Three patients experienced a sustained improvement in at least one peripheral blood cytopenia, including one patient who had a complete trilineage response. Several pre‐treatment clinical features appeared to be associated with response to ATG. All responding patients had hypoproliferative features including depressed platelet counts (<30×109/l), and a minor degree of chronic haemolysis as indicated by relatively low reticulocyte counts (<100×109/l), lactate dehydrogenase (<1000 U/l) and total bilirubin (<17μmol/l) levels. Responding patients continued to have chronic low‐grade haemolysis after their response to immunosuppression that was similar to that observed prior to treatment. The non‐responding patients had a classic haemolytic form of PNH characterized by elevated reticulocyte counts (>100×109/l), lactate dehydrogenase (>2000 U/l) and total bilirubin (>17μmol/l) levels. The impaired haemopoiesis that occurs in hypoproliferative PNH may respond to ATG treatment, but the haemolytic component of the disease, and hence the PNH clone, is not altered by immunosuppressive therapy.

Clinical and molecular aspects of 23 patients affected by paroxysmal nocturnal hemoglobinuria

“…Therapy is usually restricted to the treatment and prevention of complications. Immunosuppression with antilymphocyte or antithymocyte globulin and/or cyclosporin has been used in a few patients with controversial results [23][24][25]. The AA/PNH patient of our series who underwent immunosuppression became transfusion-independent after the second course of antilymphocyte globulin, concomitantly to the expansion of the PNH clone as recently reported by Yasunami et al [26], and he is still transfusionindependent at 3 years after treatment.…”

“…Therapy is usually restricted to blood transfusion support and iron replacement, and to treatment and prevention of complications [22]. Immunosuppression with antilymphocyte or antithymocyte globulin and/ or cyclosporin has been used in a few patients [23][24][25][26]. Moreover, it has been shown that anemia in PNH may benefit from recombinant human erythropoietin (rHu-EPO) [27][28][29][30]: reports are, however, anecdotal, and are often difficult to interpret for the concomitant administration of other drugs.…”

Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones

“…15,33 In the sub-set of patients who have an expanding PNH cell population, there may be a rationale for using this approach to treat the presumed underlying mechanism (ie auto-reactive destruction of normal stem cells), even if they are not severely pancytopenic, because they may have an on-going auto-immune process. In this series we could not detect an effect of ATG on the time-course of the size of PNH population over time.…”

Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria

“…Hemolysis in patients with PNH can be monitored by levels of the enzyme lactate dehydrogenase (LDH), which is typically elevated and can exceed 20 times the upper limit of normal during severe paroxysms. [1][2][3] There is no effective treatment for the ongoing hemolysis in PNH.…”