Friday, October 16, 2009

The Aplastic Anaemia–Paroxysmal Nocturnal Haemoglobinuria Syndrome

http://bloodjournal.hematologylibrary.org/cgi/reprint/48/1/63 (2007 article – the key to successful treatment according to the study is early transplant (within 17-100 days or original diagnosis)). Further reading evidences that siblings were matched for all participants in the study. Patients were given prednisone (10 mg sq m/day) to detect underlying leukemia. Cyclophosphamide was used alone for conditioning for engraftment. ATG or ATS and procarbazine (PCB) were given. After transplant, methotrexate was given to ameliorate potential graft-versus-host disease.

Summary
Study included 17 females transplanted who had idiopathic etiology (severe aplastic anemia from an unknown cause). Diagnosis was made within 17 weeks. Initial, PMN range was 0-1500 (avg 200), 1-23 platelets (avg. 6k), .1-1.4 retriculocytes (avg. .1%), and 40-99 nonmyeloid marrow cells (avg. 85%).

26 patients received CY alone, 10 CY plus ATG and PCB in preparation for engraftment.

Immunosuppression began within 12-97 days after diagnosis (avg. 33 days). Delays in treatments were due to INCOMPATIBLE DONORS, WAITING FOR AN AVAILABLE BED, DIAGNOSIS, INFORMED CONSENT (OF PATIENT AND FAMILY).

36 patients were to be transplanted; 2 died of sepsis during pretransplant immunosuppression; 34 patients were transplanted; 67% (24) survived with complete marrow restoration after 4-20 months (median 9 months). Of the 24, 2 are severely limited by GVHD; all others returned to regular activities within 3-12 months after transplantation.

No correlation was made to age, sex, etiology of aplasia, transplant cnter or transplant regimen.

Of the 34 engrafted, 10 died: 4 from infection, 2 from sepsis GVHD, 1 pneumonia and sepsis, 1 tuberculosis; 9 rejected graft (1 died before second transplant, 7 were retransplanted and of those 5 died for transplant failure and 2 were successfully engrafted).

Of the 24 that were successfully transplanted, 12 died. Of those, 8 rejected their grants within 4-5 weeks of transplant, 1 lost marrow activity during adenine arabinoside therapy begun 23 days post-transplant for disseminated herpes zoster, and 1 died before a second transplant could be attempted. 7 patients who rejected their initial grafts were re-transplanted; 2 were success.

31 patients were not transplanted. 7 improved (1 completely, 5 partially, 1 partially temporarily). Responses were seen within 1 to 3 months post treatment. Responses were positive in all three cell lines, but compared to transplant patients the responses were lesser. 19 patients died within 1-11 months due to 10 hemorrahaging, 7 from sepsis, and 2 from a combination of hemorrhage and sepsis.

Within 4 months, 67% of transplanted patients survived while only 36% of non-transplanted patients did so. Within 12 months, 75% of transplanted patients survived while only 22% of non-transplanted patients did so. At month 20, 75% of transplanted patients were still surviving while 1 non-transplanted patient survived, but has relapsed after 4 months and remains aplastic.

Notably, they say that the quick transplant choice of the patient played a key role in survival, and patients who were immediately transplanted without a prior non-transplant treatment failure clearly had much higher survival rates.

Study did not evaluate the role of intensive support in the management of severe aplastic anemia that is required during pretransplant treatment and during the 2-3 week period of the transplanted marrow beginning to function after transplant.

Some transplanted patients remained in protective environments and received oral non-absorbable antibiotics.

In the Seattle study of 23 aplastic anemia patients who survived more than 1 year after allogeneic mrrow transplantation, only one patient died, one has chronic GVHD, and one has almost completely recovered from chronic GVHD. The OTHER 20 PATIENTS ARE IN GOOD HEALTH WITH NORMAL MARROW FUNCTION AFTER 2 TO 4.5 YEARS POST TRANSPLANT.

STUDY SHOWS THAT PROMPT BONE MARROW TRANSPLANTATION SIGNIFICANTLY DECREASES EARLY MORTALITY OF SEVERE APLASTIC ANEMIA.


Cardeza Foundation, Philadelphia
Children’s Hospital, Boston
Children’s Hospital, Los Angeles
Children’s Hospital, Milwaukee
Children’s Hospital, Philadelphia
Children’s Hospital, St. Louis
Emory University, Atlanta
Hammersmith Hospital, London
Hematology-Oncology Associates PA.,
Plainfield
Hematology-Oncology Associates,
Providence
James Whitcomb Riley Hospital,
Indianapolis
J. HilIis Miller Health Center,
Gainesville
Johns Hopkins Oncology Center,
Baltimore
Milwaukee County General Hospital
Mount Sinai Hospital, New York City
Naval Medical Center, Bethesda
New Jersey Medical School, Newark
Peter Bent Brigham Hospital, Boston
Rhode Island Hospital, Providence
San Francisco Medical Center
St. Jude Children’s Research Hospital,
Memphis
UCLA
University of Capetown
University of Minnesota, Minneapolis
University of Kentucky, Lexington
University of Washington, Seattle
Yale University, New Haven
West Side V.A. Hospital, Chicago
A. Erslev
B. Camitta, D. Nathan,
R. Parkman
S. Siegel
J. Casper
S. Friedman, E. Schwartz
R. Ducos, A. Ragab,
H. Zarkowsky
T. Heffner, J. Keller
E.C. Gordon-Smith
D. Fnimmer
R. Damico
R. Baehner, A. Provisor
T. Dellinger
G. Santos
A. Pisciotta
R. Taub, R. Zalusky
R. Cahill, R. Hartzman,
K. Sell
T. Walters
J. Rappeport
E. Forman
J. Klock, S. Shohet
R. Strauss
S. Feig, R. Gale
D. Dubovsky, P. Jacobs
J. Kersey, W. Knivit
M. Greenwood, P. Holland
ED. Thomas, R. Storb
S. McIntosh, R. O’Brien
R. Epstein, W. Fried
USPHS FR-00l28
USPHS AM-05581
Tommy Fund
USPHS 5-M0l-RR-00888
USPHS CA-l7995
ALSAC
USPHS CA-12800-
RR00865
Minnesota Medical
Foundation
SMF-155-75
USPHS CA-10895

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