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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

Does treatment with intermittent infusions of intravenous anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura to avoid splenectomy?

Nichola Cooper, B. Michael R. Woloski, Erin M. Fodero, Maria Novoa, Melissa Leber, Juerg H. Beer, and James B. Bussel

This study explored whether repeated infusions of intravenous anti-D could al- low adults with recently diagnosed im- mune thrombocytopenic purpura (ITP) who had failed an initial steroid course to postpone and ultimately avoid splenec- tomy. Twenty-eight Rh1, nonsplenecto- mized adults with ITP diagnosed within 1 to 11 months and platelet counts 30 3 109/ L (30 000/ L) or below were enrolled. Anti-D was infused whenever the platelet count decreased to 30 3 109/L (30 000/ L) or below. “Response” was defined as a platelet increase of more than 20 3 109/ L (20 000/ L) to more than 30 3 109/L (30 000/ L) within 7 days of treatment. Patients were a median 3.5 months from

ITP diagnosis at enrollment and had re- ceived a median of 2 previous therapies, including prednisone in 26 of 28 cases. They were followed for a median 26 months. A total of 93% responded to their initial infusion of anti-D, and 68% repeat- edly responded with counts maintained above 30 3 109/L (30 000/ L) using anti-D alone. Currently, 12 (43%) of 28 patients have been off all treatment for more than 6 months without undergoing splenec-

tomy, 100 3

6

maintaining

109/L (100 000/

L).

counts above Seven continue

on treatment, 8 underwent and 1 was lost to follow-up

splenectomy, at 10 months.

One

patient

discontinued

anti-D

because

of

toxicity.

Patients

with

platelet

counts

at

least 14 3 109/L (14 000/

L) at enrollment

were more likely to discontinue treatment (P .05). Anti-D was an effective mainte- nance treatment for two thirds of Rh1, nonsplenectomized adults with ITP who had failed an initial steroid course. Inter- mittent infusions of intravenous anti-D allowed more than 40% of these adults to avoid splenectomy and to achieve stable platelet counts off all therapy, even after many months of treatment. Platelet count at study entry was the primary predictor

of outcome. (Blood. 2002;99:1922-1927)

© 2002 by The American Society of Hematology

Introduction

Immune thrombocytopenic purpura (ITP) is an autoimmune bleed- ing disorder in which antiplatelet antibodies cause accelerated platelet destruction by the mononuclear phagocytic system. Pa- tients suffering from persistent, severe thrombocytopenia are at risk for hemorrhage and have an increased mortality rate.1,2 Many patients, however, maintain a normal quality of life at below normal platelet counts with or without treatment.

Unlike children, less than one third of adults with this disease will go into sustained remission after an initial short course of steroids.2-8 The American Society of Hematology practice guide- lines for ITP in 1996 show that there is considerable variation in the recommendations of expert hematologists on the treatment of those patients who do not go into remission.2 Generally, the standard of practice for patients who cannot maintain an adequate platelet count on tapering steroids is to undergo splenectomy. In 60% to 70% of patients this restores a normal platelet count for at least 5 to 10 years.9-11 It allows those patients who respond to this procedure to avoid both the risks of low platelet counts and the toxicity of daily steroids. However, although both the site of platelet destruc- tion and the response to intravenous immunoglobulin (IVIG) have been suggested to predict response to splenectomy, there is no

universally acknowledged way to predict which patients will respond.12-16 Patients are often reluctant to be exposed to the inherent risks of surgery and the small but significant risk of overwhelming sepsis after splenectomy without a guarantee of success.17,18

Because the standard of practice has been to perform early splenectomy in steroid nonresponders, little is known of the natural history of those patients who do not go into early remission. This pilot study was designed to assess how many patients would improve their platelet counts to a level sufficient to avoid splenec- tomy if they were supported with intermittent infusions of IV anti-D to maintain their platelet count above 30 3 109/L (30 000/ mL). This platelet count was chosen as the threshold for treatment so that patients would be protected from the risks of serious hemorrhage while minimizing unnecessary treatment. IV anti-D was chosen in preference to IVIG because it is substantially less expensive, has a much shorter infusion time, and is made from a smaller donor pool. It was selected in preference to prednisone because it does not have the toxicities associated with the prolonged use of daily steroids.

A secondary aim of this study was to assess whether any clinical or biologic variables could predict which patients would respond to

From the Division of Hematology/Oncology, Department of Pediatrics, New York Presbyterian Hospital—Weill Medical College of Cornell University, NY; Cangene, Winnipeg, Canada; and Kantonsspital, Baden, Switzerland.

Reprints: Nichola Cooper/James Bussel, Division of Hematology/Oncology, P-695, Dept of Pediatrics, New York Presbyterian Hospital—Weill Medical College of Cornell University, 525 East 68th St, New York, NY 10021; e-mail: nicholacooper@yahoo.com; jbussel@med.cornell.edu.

Submitted May 25, 2001; accepted October 19, 2001.

Supported in part by a clinical research grant from Cangene, Winnipeg, Canada; the ITP Society of the Children’s Blood Foundation, New York, NY; and the Swiss National Foundation of Science, Baden, Switzerland.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. section 1734.

B.M.R.W. is an employee of Cangene Corporation.

© 2002 by The American Society of Hematology

1922

BLOOD, 15 MARCH 2002 VOLUME 99, NUMBER 6

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