2003; baxter - Supplements - Haematologica

IV International Workshop on Immune Tolerance in Hemophilia 97Table 9. Immunosuppressive therapy.Therapy Induction: final results Relapsen CR PR F n CR PR FSteroid 28 27 2 2 4 2 1 1Steroid + immunoglobulins 4 3 0 1 1 1 0 0Steroid + cyclophosphamide 13 10 1 2 2 1 1 0Cyclophosphamide 6 4 1 1 1 1 0 0Steroid + azathioprine 8 6 1 1 2 1 1 0Azathioprine 3 2 1 0 1 1 0 0Steroid + melphalan 1 1 0 0 0 0 0 0Cyclosporine 2 2 0 0 0 0 0 0Total 65 52 6 7 11 7 3 1CR = complete remission ; PR = partial remission ; F = failure ; R = relapse.Table 11. Immunosuppressive therapy in patients with postpartuminhibitor.Therapy n 1 st CR PR F R 2 nd CRNone 2 2Steroid 10 7 3 3* 3Steroid + cyclophosphamide 1 1Cyclophosphamide 1 1 1° 1Steroid + azathioprine 2 2 1 § 1Steroid + high-dose immunoglobulins 4 3 1 # 1^ 1Total 20 14 3 6 6CR = complete remission; PR = partial remission; F = failure; R = relapse.*CR obtained in PR patients, 1 with azathioprine, 1 withsteroid + cyclophosphamide, 1 with no therapy; # steroid + Ig for 6 months;°azathioprine; § steroid + azathioprine; ^steroid + cyclophosphamide.Table 10. Characteristics of the women with post-partuminhibitor formation in relation to the treatment for bleedingcontrol (median, range and mean±SD).Patients requiring Therapy N. therapyNumber 11 9Median (range) time to bleeding(relation to delivery) (days) 8.5 (1-150) 90 (1-150)Type of bleeding Methrorragia Mildhematomata ecchymosesMean (SD) inhibitor titer (BU/mL) 7.5 (7.0) 13.5 (11.8)^Mean (SD) Hb (g/dL) 7.5 (2.1) 10.3 (2.1)^Number of patients requiring transfusions 8 2^p = ns.delayed in the patients not requiring treatment. In2 patients the inhibitor disappeared spontaneouslyafter 2 and 4 months. Eighteen patientsreceived immunosuppressive therapy as detailedin Table 11: prednisone alone in 10 patients, combinedwith other agents in 7. CR and PR wereobtained in 14 (78%) and 3 (16%) patients,respectively (overall response rate 94%). In onepatient the inhibitor was unchanged (2.5 BU)after a follow up of 48+ months. The median timeto obtain the first complete remission was 2.7months (range 0.5-36) and the median time ofthe treatment was 4.0 (range 1-18) months. In 1patient the inhibitor persisted at a low titer duringthe treatment and disappeared thereafter. Sixwomen relapsed after a median time of 16months (range 6-24 months) and were rescuedwith additional treatment. The majority of thepatients who achieved 1 st or 2 nd CR receivedsteroids alone or in combination. The time to thefirst CR was independent of the baseline inhibitortiter: median 3 months (range 0.5-18) in 8patients with inhibitor titer 10 BU. The inhibitor titerand the time to response were not different in thepatients who relapsed (median inhibitor titer 6.5BU - range 3.2-140 and median time to response2.7 months - range 2-36) and in those who didnot relapse (median inhibitor titer 8.0 - range 1.6-32 and median time to response 2.0 months –range 0.5-15). The survey did not yield informationon the neonates.DiscussionThe total number of cases in our survey is lowerthan expected, considering the 15 year-period,probably because of underreferral to the centers.The results of this retrospective survey could,therefore, be biased. Age, percentage of idiopathiccases (47%) and primary diseases are similarto those in previous reports. 2,4,6 In 31 patients(33%) (15 with idiopathic inhibitors and 16with concomitant disease), bleeding ensued afteran intervention or after a trauma. The prolongedaPTT was known prior to surgery and also in thepost partum patients but was overlooked. Thecorrect evaluation could have avoided the surgicalbleeding and, possibly, the hysterectomies.Twenty-three patients, including 9 post partumwomen, did not require therapy for the bleeding.The bleeding was mild and self-limited as indicatedby clinical signs and hemoglobin level(Tables 4 and 6). In our survey the inhibitor titerwas not correlated with either the intensity ofbleeding or the response to therapy but such correlationshave been reported by other investigators.7,8 An anamnestic response was recorded in8 cases unrelated to pregnancy but is at variancewith other reports on the post-partum period. 8,9The variety of agents used to control the bleedingprecludes any evaluation of the appropriate initialtreatment. A similar observation refers to theimmunosuppressive therapy. Prednisone was thepreferred agent both in induction and in relapse.A response (CR+PR) was obtained in the majorityof cases. The data are in agreement with thosealready published. 2,9 Eight patients died becausehaematologica vol. 88(supplement n. 12):september 2003