Hans-Georg Klingemann

Kidneys and Urinary Tract

In contrast to the liver, the kidneys are less frequently the primary target of a pathological event after bone marrow transplantation. Acute and chronic GVHD do not obviously affect the kidney, although some cases of nephrotic syndrome possibly related to GVHD have been reported. A specific disease entity related to chemo/radiotherapy-induced damage has not been observed; however, it is likely that a subclinical degree of tubular damage occurs during the conditioning regimen. Renal impairment is predominantly secondary to circulatory disturbances associated with VOD, septicemia or hypovolemic shock, or is related to drugs frequently used post-transplant that can injure the tubular system (such as cyclosporine and amphotericin). In general, the severity of renal impairment can range from mild pre-renal insufficiency to acute oliguric (or anuric) renal failure. Furthermore, hemorrhagic cystitis secondary to drug toxicity or infections can occur in up to 30% of all transplant recipients and can cause significant morbidity and mortality after marrow transplantation.

Side Effects of Conditioning Regimens

Despite the reconstitutive effects of marrow transplantation on hematopoiesis, severe hematologic and non-hematologic toxicity is produced by the myeloablative conditioning regimens commonly used to condition patients. Specific toxicities depend on the agents employed, their dose and schedule as well as the patient’s overall clinical condition, co-morbid illness, prior treatment, disease status, excretory-organ function, concomitant medications, etc. Disease status is a particularly important prognostic factor for toxicity, as it is a rough but useful gauge of the extent of prior therapy and the resultant degree of organ damage. Moreover, patients with advanced disease status will tend to tolerate therapy less well for other reasons related to the presence of advanced disease.

Preparation for Marrow Transplantation

This section deals with the mechanics of preparing for marrow transplantation. Some patients will be evaluated by the Transplant Team before the results of tests that indicate eligibility for transplantation are available, while other patients will arrive at the Transplant Center with all test results known, and having been fully informed of the procedure. In any case, it is necessary to discuss with the patient the important aspects of transplantation shortly before the conditioning regimen begins. An overall schema of this procedure is offered in Table 4. (Since most transplants are from normal donors, this approach is emphasized. However, the use and indeed desirability of autologous marrow transplantation is discussed below.)

Acute Graft-Versus-Host Disease (GVHD)

With a successful marrow transplant, the recipient’s lymphohemopoietic cells are replaced by donor-derived cells. Thus, in contrast to solid organ transplantation where the recipient’s immune system remains in place and attempts at immunosuppression are aimed at preventing the reaction of recipient cells against the transplanted organ, a double-barrier exists in marrow transplantation: transplanted marrow may fail to reconstitute successfully hemopoiesis in the recipient (graft failure due to immunological mechanisms or other factors) or donor lymphocytes may attack recipient tissue. While graft failure has generally been a problem only with HLA incompatible transplants, after marrow T-cell depletion and in some patients sensitized by prior transfusions, GVHD has been a major problem with all allogeneic transplants. We have to assume that in all instances of marrow transplantation an interaction between donor and host cells (graft-vs-host reaction) takes place. However, it was noted in early experiments that syngeneic, i.e., genetically identical marrow, could be transferred to a pretreated recipient without any clinically recognizable adverse reaction. In contrast, when marrow from an allogeneic donor was used a clinical syndrome developed which was originally termed secondary disease. This syndrome, subsequently called GVHD, is manifested mostly in skin, liver, and intestinal tract, although other targets such as the conjunctivae can be involved as well (see Table 15).

Central Nervous System

The spectrum of CNS complications after marrow transplantation is notable for lack of direct involvement of the brain (in contrast to many other organs) by acute GVHD. The following major CNS complications have been observed: Leukoencephalopathy Drug-induced neurotoxicity Infections Hemorrhage Recurrence of malignancy Metabolic encephalopathy

Neuroendocrine Function, Growth and Development

Radiochemotherapy affects not only the intended target cells and tissues, i.e., lymphohemopoietic cells and tumor cells, but the entire organism. The most important factor is radiation. Current knowledge suggests that adverse effects are fewer, less severe or shorter lasting in patients conditioned with chemotherapy alone.

Treatment Planning and Timing of Transplantation

Marrow transplantation is an established modality and may represent the treatment of choice for a given patient. Hence, consideration of transplantation should be part of treatment planning early in the patient’s course. However, there must be no misunderstanding: although some 30,000 patients have been transplanted, marrow transplantation remains a complex and expensive therapy. Results depend upon factors such as pretransplant therapy, disease stage, patient age, histocompatibility of donor and patient, donor and patient sex, allosensitization of the donor, donor age, and the patient’s overall medical condition.

Other Delayed Complications

Conditioning regimens used for marrow transplantation, chronic GVHD and its treatment affect all organs, and side effects in addition to those classically recognized must be expected.

Cost and Availability of Transplantation

Bone marrow transplantation is a complex and expensive procedure. Estimates provided by different transplant centers in the USA, for example, range from

A guide to bone marrow transplantation

150,000 to