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Eighty percent of allogeneic and nearly all autologous transplants have been undertaken for treatment of malignancy. Effects of donor-host immune incompatibility are routinely encountered after allogeneic marrow transplantation. Graft-versus-host disease, graft rejection and infection due to immune dysfunction remain major causes of treatment failure. Bone marrow transplantation has now progressed to a therapeutically effective modality which is now standard therapy for selected diseases. Improved outcomes from bone marrow transplantation have been documented during the past decade reflecting progress primarily in prevention and treatment of transplant complications and less in ability to bone marrow transplantation, bone marow transplantation, transplant.
| Hematologic | Solid Tumors |
|---|---|
| Acute lymphoblastic leukemia | Ewing's sarcoma |
| Acute myelogenous leukemia | Neuroblastoma |
| Chronic myelogenous leukemia | Germ cell tumors |
| Non-Hodgkin's lymphoma | Ovarian cancer |
| Hodgkin's disease | Breast cancer |
| Multiple myeloma | |
| Chronic lymphocytic leukemia | |
| Myelodysplastic syndromes |
Syngeneic marrow grafts, taken from genetically identical twins, are ideal from an immunological standpoint. However, such donors are rare, and most marrow donors are HLA-A, -B, -DR, and -D identical siblings. Each
Autologous transplantation requires cryopreservation of viable marrow cells usually harvested while the patient is in chemotherapy-induced remission. This involves freezing it with a cryoprotective agent and storage in liquid
This section deals primarily with results of transplants from HLA-matched sibling donors and with autologous transplants.
Initially, allogeneic BMT was used as a last resort for patients with acute myeloid leukemia. Approximately 15% of these patients became long-term survivors and the relapse rate was 65%. Improved results were seen when
As with AML, allografting was first employed in patients with advanced acute lymphoblastic leukemia (ALL) and results were similar. Relapse-free survivals of 11% to 23% have been seen for ALL patients treated in relapse. Allografting in patients who fail to achieve a first remission leads to a 23% survival and
In children with ALL, the excellent results of conventional chemotherapy means that BMT is reserved for relapsed patients or first remission patients with adverse risk factors. BMT is superior to chemotherapy in children who
Because chronic myelocytic leukemia (CML) is a stem cell disorder, most interest has focused on allogeneic transplantation with little evidence to date that autologous transplant has curative potential. Results of allografting for CML in blast crisis are similar to those with advanced acute leukemia with long-term survival of
Currently BMT is the only curative treatment for CML, although some patients treated with alpha interferon may
Chronic lymphocytic leukemia (CLL) is a disease of the elderly but occasionally younger patients are candidates for transplant. Because it is an indolent form of leukemia, there is a reluctance to use aggressive strategies early in
Because conventional chemotherapy may cure a significant proportion of patients with Hodgkin's disease and high or intermediate grade non-Hodgkin's lymphoma (NHL), BMT is usually reserved for relapsed patients. After relapse, most patients cannot be cured by chemotherapy and BMT is usually the treatment of
This term refers to a heterogeneous group of clonal marrow failure syndromes found mostly in the elderly and with a predisposition to evolve to refractory AML. Conventional treatment is essentially supportive, and
Myeloma is generally considered to be a chemo-sensitive tumor but median survival remains only 2 to 3 years with conventional therapy. Increasingly, BMT is being used for younger patients. Autografting is associated with high relapse rates but continues to be widely used to prolong survivals and
Marrow grafting has been successful in small numbers of patients with myelofibrosis, hairy cell leukemia, and hemophagocytic lymphohistiocytosis.
In recent years the most dramatic change in the use of BMT has been the greatly expanded use of autografting for breast cancer. The use of PBSC combined with well tolerated conditioning regimens has facilitated an increased use of high-dose therapy for metastatic (stage IV) disease. However, efficacy of BMT in this patient group is
Pilot studies of autografting have been reported for chemo-sensitive solid tumors including neuroblastoma, melanoma, ovarian carcinoma, germ cell tumors, childhood sarcomas, brain tumors and small cell lung cancer, usually after failure of other therapy. Results overall have been poor, with the exception of
Data from animal and human transplantation studies have shown that donor-recipient HLA disparity adversely affects engraftment, graft rejection, GVHD and immune reconstitution. Nevertheless because only 35% to 40% of
HLA-Nonidentical Related Donors
These donors are usually HLA haploidentical with the patient and are phenotypically matched at 0, 1, 2, or 3 HLA loci on the nonshared haplotype. Transplant-related complications increase commensurate to the degree of
Unrelated Donors
Molecular studies of several HLA loci have shown sequence polymorphisms within serologically defined antigens. This indicates that the likelihood of finding unrelated donors who are genotypically HLA-matched is remote. Computerization of HLA-typing data has facilitated development of large donor registries in North America and
Complications of transplant depend to some extent on patient age, type of transplant, underlying disease, and pre-existing medical problems. The principal complications of BMT for malignancy are listed in
Recovery to normal granulocyte and platelet levels is usual by day 40-50, and to normal hematocrit values by day 60-90. Recovery of monocytes and return of bronchoalveolar and hepatic macrophages are equally prompt.
Viral and Protozoan Infections
The most serious infections during the immediate posttransplant months are of viral origin. Most important is cytomegalovirus (CMV) infection which manifests primarily as gastrointestinal infection or pneumonia. CMV infection was seen in about 75% of patients seropositive for CMV before transplant and usually within 3 months of transplant. Most cases appear to be due to a reactivation of latent virus in host or transfused hematopoietic cells.
Graft rejection is rare in recipients of unmodified HLA-identical sibling marrow (< 1% incidence). More often, poor graft function arises due to drug toxicity or related to infection. When incriminating drugs are discontinued
Acute Graft versus Host Disease
Acute GVHD is caused by alloreactive T cells directed against non-MHC histocompatibility antigens presented by host antigen-presenting cells or alternatively directed against MHC when HLA incompatibility exists. Cytokines
The clinical and histological criteria for acute GVHD have been described in detailed reviews. There is
Recurrent malignancy is a major cause of treatment failure occurring in 20% to 80% of cases. Almost always this