الفهرس 
Histocompatibility system (HLA)Only 14 pages are availabe for public view
 |  | from | 136 |  |  |
| | | from | 136 | | |
Abstract
- 95 -
SUM MAR Y
Bone marrow transplantation has been shown to provide
a means for curative correction of a number of lethal
Congenital and acquired disorders of the hematopoietic
and lymphoid systems •
Marrow transplantation is the therapy of choice for
patients with severe aplastic anaemia at the time of diagnosis
and severe combined immunodeficiency • Marrow transplantation
has emerged as a highly promising approach to
the treatment of high risk forms of leukemia, particularly
when applied to patients in remission early in the course
of their disease. It has been evaluated in the treatment
of chronic myelogenous leukemia, non Hodjkin’s lymphomas,
neuroblastoma and other solid tumours ana in a number of
immunodeficiencies and inborn errors of metabolism •
Depending on the genetic relationship between the
donor and recipient, there are three typeS of transplants
performed in clinical bone marrow transplantation. Synge_
neic refers to transplants between genetically identical
members of the same species, such as identical twins
allogenic refers to transplants in which the donor and
_._----- - - -
- 96 -
recipient are genetically dissimilar members of the
same species, usually siblings, and autologous refers
to those transplants where patients are transplanted
with their own previously harvested marrow • The majority
of bone marrow transplants at present are allog_
enic .
Except in patients undergoing syngeneic transplants
and in those with severe combined immunodefi_
ciency, immunosuppression is required to permit engraftment
of donor marrow • Patients with aplastic anaemia
who have not been transfused before transplant_
ation are given cyclophosphamide alone but those who
have been transfused are given cyclophosphamide and
total lymphoid irradiation or cyclophosphamide and
addition of viable donor buffy coat cells.
Patients with neoplasms require total body
irradiation or addition of high dose chemotherapy to
eradicate existing disease, and to create space wi thin
hast marrow to allow the transplanted stem cells to
proliferate. Because most tumour cells repair radiation-
induced DNA damage poorly as compared to
most normalcells, fractionating TBI permits the
- 97 -
administration of higher total doses.
Bone marrow donors Qre selected by human leuko_
cyte antigen (HLA) typing • Hiatocompatibility between
donor and recipient is established by demonstrating
HLA-A, B, C, and DR identity and mutual nonreactivity
in mixed lymphocyte cUlture. At present, transplants
are carried out mostly between histocompatible siblings.
Practically,this translates into finding matches for
only about 35 to 40 percent of potential transplant
candidates.
After appropriate patient and donor selection
the recipient may undergo a pretranaplant evaluation
of the status of the underlying disease and the funct_
ion of various organ sYstems that may be adversely aff_
ected during and after transplantation • Any existing
infection is treated vigorously. Many patients receive
trimethoprim - sUlfamethoxazole for 10 to 14 days prior
to their transplants to prevent pneumocystis carinii
pneumonia.
In patients with aplastic anaemia, transfusions
of blood products should be limited before tra~splanta_
tion since they induce sensitization and increase the
- 98 -
likelihood of graft rejection. The marrow donor or
other family members should not serve as pre transplant
blood component donors.
Following infusion of the marrow inoculum, msna_
gement of the recipient is aimilar to the case of any
patient with prolonged Pancytopenia following intensive
anticancer treatment • The risk of ~xogenous infection
is minimized by housing patients in strict reverse isolation
and decontamination in a laminar air flow rooms
Because of the risk of infection from the patients own
bacterial flora, the patients may be given oral nonabsorbable
antibiotics and fed a sterile diet • Micro_
bicidal agents are Used to bathe the patients, and
antibacterial and antifungal creams may be applied to
skin folds and orifices. Transfusions of platelets
and red blood cells are necessary until the donor bone
marrow becomes fUlly functional and hemstologic recon_
stitution is achieved within 4 to 6 weeks following inf_
uSion
One of the major problems encountered in bone
marrow transplantation is the graft rejection especially
in mUltiply transfused patients with aplastic anaemia,
- 99 _
the incidence of graft rejection is thus quite minimsl
in untransfused patients with aplastic ansemia • Sensi_
tization is less likely to occur in patients with leuk_
emia who receive transfusion support because of the
chronic immunosuppression induced by their antileUkemic
chemotherapy • The high rejection rate has been marke_
dly reduced by augmenting the pre transplant immuno_
suppressive regimens with low doses of TBI , total
lymphoid irradiation, procarbazine, anti thymocyte globUlin
(ATG),or additional donor peripheral blood bUffy
coat cells.
GVHD remains one of the major obataclea to SUccessful
allogenic BMT • Because of difficulty in treating
it once it has occurred, attention has been directed toward
prevention several approaches have been investiga_
ted in attempts to decrease its incidence, these incl_
Ude Using methotrexate early after transplantation and
on a prolonged schedule or methotrexate, anti thymocyte
globulin, and prednisone or’ immunosuppression wi th cy cLn ,
sporin A • There are two types of Graft versus host didisease
• The acute GVHD and the chronic GVHD • Acute
GVHD develops wi thin the first 100 dsys post transplant,
and occurs in 30 to 70 percent of sll patients.
- 100 _
The chronic form of GVHD begins 6 to 18 months
after transplantation and occurs in 15 to 40 per cent
of the long term survivors of HlA matched transplant
It may follow acute GVHD or occur de novo
Because of the myeloablative and immunosuppre_
ssive therapy used prior to BMT and the prolonged period
of immunodeficiency that fOllows it, infections
frequently complicate bone marrow transplantation and
account for a sUbstantial number of the fatalities
among transplant recipients.
During the immediate post transplant period ,
patients are neutropenic and lymphopenic and may develop
septicemia and localized bacterial or fungal
infections, or reactivate latent herpes simplex or
herpes zoster infections. Interstitial pneumonia develops
in 35 to 40 per cent of all a.llogenic marrow
transplants and continues to be a major obstacle to
the long-term survival of many transplant recipients.
Recurrence of leukemia following marrow graft_
ing continues to be a major complication,particularly
in patients with Acute lymphoblastic leUkemia (All).
- 101 -
The risk of leukemic relapse have been reduced,mainly
in patients who had acute GVHD and in whom chronic
GVHD developed subsequently, and exert an antileukemic
effect.
_._-._~------------- r--