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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

The Hematopoietic Stem Cell Graft

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.

Acute Myeloid Leukemia

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

Acute Lymphoblastic Leukemia

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

Chronic Myelocytic Leukemia

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

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 

Multiple Myeloma

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 

Other Hematologic Malignancies

Marrow grafting has been successful in small numbers of patients with myelofibrosis, hairy cell leukemia, and hemophagocytic lymphohistiocytosis.

Breast Cancer

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 

Other Solid Tumors

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 

HLA-Nonidentical Marrow Grafts

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 of Hematopoiesis and Immune System

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.

Opportunistic Infections

Bacterial and Fungal Infections

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.

Immunological Problems

Graft Failure

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

Clinical Features.

The clinical and histological criteria for acute GVHD have been described in detailed reviews. There is

Recurrence of Malignancy

Incidence and Origin of Recurrent Disease

Recurrent malignancy is a major cause of treatment failure occurring in 20% to 80% of cases. Almost always this