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Jeanne Lusher

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Jeanne Lusher

Jeanne Marie Lusher, M.D. (June 9, 1935 - September 13, 2016)[1] was an American physician, pediatric hematologist/oncologist, and a researcher in the field of bleeding disorders of childhood, and has served as the director of Hemostasis Program at the Children's Hospital of Michigan until her retirement on June 28, 2013.

Early life and education

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Jeanne Lusher was born in 1935 in Toledo, Ohio, USA. Her family moved to Cincinnati, Ohio when she was three years old, and Lusher grew up there. Although her mother had French Canadian background and spoke French with her relatives, Lusher never learned French. During high school, she was interested in music, and played several instruments in the school band and orchestra, but later decided to pursue a career in science. Lusher never married.

Lusher received her medical degree from the University of Cincinnati in 1960, and went on to do internship at the George Washington University Hospital in Washington D.C., and pediatric residency and chief residency at Charity Hospital in New Orleans, Louisiana. During her pediatric residency at Charity Hospital, Lusher took care of a young girl with hemophilia (a rare occurrence for an X-linked recessive disorder), which stimulated her interest in blood coagulation and bleeding diseases. Her interest in bleeding disorders would later a become a lifelong dedication. In order to increase her knowledge in pediatric hematology, Lusher went to Children's Hospital of Michigan, Detroit for a brief rotation with Dr Wolf W. Zuelzer, a prominent pediatric hematologist then. Upon her return to Charity Hospital, she took on the care of children with blood diseases and cancers there.

At the completion her residency, Lusher returned to Children's Hospital of Michigan, Detroit, for a fellowship in pediatric hematology/oncology (1964-1966). She completed the third year of her fellowship with Teresa Vietti at Washington University in St Louis, where she focused on pediatric oncology and the treatment protocols of the Southwest Oncology Group (SWOG). Dr Lusher returned to Detroit in 1966, this time as a staff pediatric hematologist/oncologist.

Research career

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Lusher's work focused mainly on Immune Thrombocytopenic Purpura (ITP) and hemophilia. For translational research, Lusher collaborated with Professor Marion I Barnhart from the physiology department of the Wayne State University School of Medicine.[2]

1- Immune Thrombocytopenic Purpura: Lusher and Zuelzer presented a comprehensive description of the natural history of ITP in children as early as in 1966.[3] Lusher and her colleague Indira Warrier were among the first to use intravenous immunoglobulin (IVIG) for the treatment of ITP in children, and reported its therapeutic effect in 1984.[4] They also reported that IVIG could be an alternative to splenectomy in patients with the chronic form of childhood ITP.[5] However, Lusher and colleagues also recognized that acute ITP in childhood was a self-limited condition, and did not necessarily require pharmacologic treatment.[6]

2- Hemophilia:

Lusher started the first comprehensive hemophilia program at the Children's Hospital of Michigan in 1966.[7] The available treatment for hemophilia at the time included transfusion of large volumes of fresh frozen plasma to replenish the missing clotting factors. Cryoprecipitate, and later in 1970, lyophilized factor VIII concentrates became available for the treatment of hemophilia A.[8] One of the most frustrating complications in the treatment of hemophilia then, was the development of inhibitors to Factor VIII or Factor IX, which neutralized the activity of the factor given for treatment. Prothrombin complex concentrates had been used since the 1970s as a bypassing agent in a few anecdotal cases of hemophilia with inhibitor development, but their efficacy had not been fully established.[9] Lusher was able to demonstrate their efficacy in the treatment of joint bleeding in hemophilia in two multi-center studies in the early 1980s.[10][11] Lusher later conducted the first studies on the use of recombinant factor VIIa in the treatment of bleeding episodes in patients with hemophilia.[12][13][14] As this product was safer than prothrombin complex concentrates, and could be administered at home by the patients themselves, she and colleagues promoted its use in patients with inhibitors to treat bleeding episodes.[15][16]

The hemostatic efficacy of desmopressin, an analog of vasopressin, was first discovered in Italy in 1977 by Mannucci and colleagues.[17] This substance, when administered intravenously or intranasally, elevates factor VIII levels transiently, and was found to be useful in treating minor bleeding episodes or in preventing postoperative hemorrhage when given prior to minor surgical operations in patients with mild to moderate hemophilia or some types of von Willebrand disease. Lusher introduced the hemostatic use of desmopressin to the United States. After first trying it on herself and her colleagues, and documenting the rise of factor VIII levels, she proceeded to use it in patients with hemophilia and von Willebrand disease, and reported its efficacy.[18] Desmopressin was finally approved for use in hemophilia and von Willebrand disease by the FDA in 1984.[19][20]

In the 1980s, Lusher and her colleagues recognized an immune dysfunction in patients who received repeated blood transfusions, including patients with hemophilia. Specifically, helper/suppressor lymphocyte ratios were diminished, a hallmark of acquired immunodeficiency syndrome (AIDS) in multi-transfused patients.[21] The loss of countless patients with hemophilia to infection with Human Immunodeficiency Virus (HIV) and hepatitis C (acquired through transfusion of plasma or plasma-derived factor VIII concentrates) in the 1980s was a devastating blow to the hemophilia community. Lusher therefore participated in several pioneering multi-center studies that tested pasteurized factor concentrates, which eliminated HIV transmission.[22] Lusher also addressed the social stigma associated with the HIV infection, and demonstrated that HIV was not transmitted to the household members of infected patients.[23]

Once the factor VIII concentrates that were manufactured using recombinant DNA technology became available, Lusher conducted one of the first clinical trials using these concentrates in the treatment of hemophilia patients, and showed its efficacy.,[24][25] Lusher promoted prophylactic treatment in patients with hemophilia (as opposed to on-demand treatment only during bleeding episodes) as she and other researchers had shown that this strategy drastically reduced complications such as joint damage after repeated bleeding episodes in patients with hemophilia.[26] Lusher, along with other researchers, successfully used recombinant factor VIII concentrates for immune tolerance induction in patients who had developed inhibitors.[27]

Lusher and colleagues reported on the peculiar side effect profile (i.e., anaphylaxis, nephrotic syndrome) of recombinant factor IX in patients with hemophilia B.[28][29][30]

Lusher also participated in a multi-center phase 1 trial of Factor VIII gene therapy.[31]

Recognition

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Lusher served as the Marion I. Barnhart Hemostasis Research Professor and Distinguished Professor of Pediatrics at Wayne State University; the director of the Hemophilia, Hemostasis and Thrombosis Program and the medical director of the coagulation laboratories at the Children's Hospital of Michigan. She was the recipient of the Kenneth Brinkhous Physician of the Year Award by the National Hemophilia Foundation in 1993, the American Society of Pediatric Hematology/Oncology Distinguished Career Award in 2002,[32] and the Hemostasis & Thrombosis Research Society, Lifetime Achievement Award in 2009.[33]

References

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  1. ^ "Jeanne Marie Lusher M.D. Obituary - Visitation & Funeral Information".
  2. ^ "Prognosis E-News". Prognosis.med.wayne.edu. 2013-07-05. Retrieved 2013-09-05.
  3. ^ Lusher JM, Zuelzer WW. Idiopathic thrombocytopenic purpura in childhood. J Pediatr 1966;68:971-9.
  4. ^ Warrier I, Lusher JM. Intravenous gamma globulin treatment for chronic idiopathic thrombocytopenic purpura in children. Am J Med 1984;76:193-8.
  5. ^ Warrier IA, Lusher JM. Intravenous gammaglobulin (Gamimune) for treatment of chronic idiopathic thrombocytopenic purpura (ITP): a two-year follow-up. Am J Hematol 1986;23:323-8.
  6. ^ Lusher JM, Emami A, Ravindranath Y, Warrier AI. Idiopathic thrombocytopenic purpura in children. The case for management without corticosteroids. Am J Pediatr Hematol Oncol 1984;6:149-57.
  7. ^ Ravindranath Y. The American Society of Pediatric Hematology/Oncology Distinguished Career Award goes to Jeanne Lusher, M.D. J Pediatr Hematol Oncol 2002;24:169-71.
  8. ^ Lusher JM. Development and introduction of recombinant factor VIII--a clinician's experience. Haemophilia 2012;18:483-6.
  9. ^ Sonoda T, Solomon A, Krauss S, Cruz P, Jones FS, Levin J. Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII. Blood 1976;47:983-9.
  10. ^ Lusher JM, Blatt PM, Penner JA, et al. Autoplex versus proplex: a controlled, double-blind study of effectiveness in acute hemarthroses in hemophiliacs with inhibitors to factor VIII. Blood 1983;62:1135-8
  11. ^ Lusher JM, Shapiro SS, Palascak JE, Rao AV, Levine PH, Blatt PM. Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII: a multicenter therapeutic trial. N Engl J Med 1980;303:421-5.
  12. ^ Macik BG, Lindley CM, Lusher J, et al. Safety and initial clinical efficacy of three dose levels of recombinant activated factor VII (rFVIIa): results of a phase I study. Blood Coagul Fibrinolysis 1993;4:521-7.
  13. ^ Lusher JM. Recombinant factor VIIa (NovoSeven) in the treatment of internal bleeding in patients with factor VIII and IX inhibitors. Haemostasis 1996;26 Suppl 1:124-30.
  14. ^ Hedner U. History of rFVIIa therapy. Thromb Res 2010;125 Suppl 1:S4-6.
  15. ^ Key NS, Aledort LM, Beardsley D, et al. Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors. Thromb Haemost 1998;80:912-8.
  16. ^ Mehta R, Parameswaran R, Shapiro AD. An overview of the history, clinical practice concerns, comparative studies and strategies to optimize therapy of bypassing agents. Haemophilia 2006;12 Suppl 6:54-61.
  17. ^ Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases. Lancet 1977;1:869-72.
  18. ^ Warrier AI, Lusher JM. DDAVP: a useful alternative to blood components in moderate hemophilia A and von Willebrand disease. J Pediatr 1983;102:228-33.
  19. ^ "ARMOUR's STIMATE (DESMOPRESSIN) APPROVED FOR HEMOPHILIA A :: "The Pink Sheet" :: Elsevier Business Intelligence". Elsevierbi.com. 1984-04-09. Retrieved 2013-09-05.
  20. ^ Brody JE. "Dangers of little-known clotting disorders". The Herald Journal, 1995 September 7.
  21. ^ Kaplan J, Sarnaik S, Gitlin J, Lusher J. Diminished helper/suppressor lymphocyte ratios and natural killer activity in recipients of repeated blood transfusions. Blood 1984;64:308-10.
  22. ^ Smith KJ, Lusher JM, Cohen AR, Salzman P. Initial clinical experience with a new pasteurized monoclonal antibody purified factor VIIIC. Semin Hematol 1990;27:25-9.
  23. ^ Lusher JM, Operskalski EA, Aledort LM, et al. Risk of human immunodeficiency virus type 1 infection among sexual and nonsexual household contacts of persons with congenital clotting disorders. Pediatrics 1991;88:242-9.
  24. ^ Lusher JM, Arkin S, Abildgaard CF, Schwartz RS. Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. Safety, efficacy, and development of inhibitors. Kogenate Previously Untreated Patient Study Group. N Engl J Med 1993;328:453-9.
  25. ^ Haney DQ. Genetic engineers make clotting agent for hemophiliacs. The Daily Gazette 1990 December 27.
  26. ^ Lusher JM. Prophylaxis in children with hemophilia: is it the optimal treatment? Thromb Haemost 1997;78:726-9.
  27. ^ Unuvar A, Warrier I, Lusher JM. Immune tolerance induction in the treatment of paediatric haemophilia A patients with factor VIII inhibitors. Haemophilia 2000;6:150-7.
  28. ^ Warrier I, Ewenstein BM, Koerper MA, et al. Factor IX inhibitors and anaphylaxis in hemophilia B. J Pediatr Hematol Oncol 1997;19:23-7.
  29. ^ Ewenstein BM, Takemoto C, Warrier I, et al. Nephrotic syndrome as a complication of immune tolerance in hemophilia B. Blood 1997;89:1115-6.
  30. ^ DiMichele D. Inhibitor development in haemophilia B: an orphan disease in need of attention. Br J Haematol 2007;138:305-15.
  31. ^ Collins H. Early trial of gene therapy for hemophilia goes well. Pittsburgh Post-Gazette 2000 March 2.
  32. ^ "biography - Jeanne Lusher, MD (Michigan)". Nlm.nih.gov. 2011-01-25. Retrieved 2013-09-05.
  33. ^ ":: Hemostasis & Thrombosis Research Society ::". Htrs.org. Retrieved 2013-09-05.
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