Hematopoietic Cell Transplantation

Management of relapse

Despite the intensity of the preparative regimen, some patients relapse after receiving an allogeneic BMT. For patients with CML, withdrawal of immunosuppression to allow for an augmented graft-vs-tumor effect sometimes leads to remission. Other patients with CML may respond to post-transplantation interferon or reintroduction of drugs such as imatinib(Drug information on imatinib) (Gleevec) or dasatinib(Drug information on dasatinib) (Sprycel), which appears to be a useful approach. Intriguingly, infusion of donor lymphoid cells into patients with CML is an effective means of inducing hematologic and cytogenetic responses in those who have relapsed after transplantation; this approach has led to complete and durable remissions.

Some patients with AML have responded to either infusion of donor stem cells or the combination of chemotherapy and donor stem cells. Patients with acute lymphoblastic leukemia have had the lowest response rate to this strategy. Patients who develop myelodysplasia after autologous transplantation can sometimes be successfully treated with reduced-intensity allogeneic transplant to restore normal hematopoiesis and cure the myelodysplastic syndrome.

Second malignancy after HCT

Patients undergoing transplantation are at risk for developing a second cancer. For those undergoing autologous transplantation, particularly for treatment of lymphoma and Hodgkin lymphoma, the most common cancer is myelodysplasia/AML, which occurs in up to 10% of patients, usually within 3 to 7 years after transplantation.

Risk factors for the development of myelodysplasia/AML after transplantation include the number of prior chemotherapy and radiation therapy treatments, specific drugs such as alkylating agents or topoisomerase inhibitors, difficulty in mobilizing stem cells, persistent cytopenias after transplantation, and use of TBI in the transplant preparative regimen. All patients should undergo cytogenetic screening of the marrow prior to stem cell collection and should be followed for this complication after recovery from transplantation.

Patients undergoing either autologous or allogeneic transplantation are also at risk for the development of solid tumors up to 20 years after transplantation. The risk is greater in patients receiving an allogeneic transplant. The most common tumors are related to the skin, but both common (breast, lung, and colon) and less common (sarcoma) tumors have been seen. As part of their long-term follow-up, all patients require screening for this complication to diagnose the cancer in its earliest stage.

Additional long-term effects

Chronic GVHD

Given the increasing numbers of patients who are long-term survivors of allogeneic transplantation, both primary care physicians as well as medical oncologists are seeing patients with chronic GVHD as part of their practice. Thus, recognition of the manifestations of chronic GVHD and its complications are an important component of long-term care, as well as close coordination with the transplant unit for their management. Chronic GVHD may evolve from acute GVHD that develops early after transplantation, but may also occur after resolution of acute GVHD or it may occur without prior acute GVHD, often after a patient has returned to their primary care physician.

Common manifestations include lichenoid changes of the skin and mucous membrane, vitiligo, periorbital hyperpigmentation, odynophagia, nail dysplasia, keratoconjunctivitis, xerostomia, alopecia and, most important, susceptibility to infection. Hence, there is the need for prevention strategies, as well as immunizations as previously mentioned. In women, vaginal strictures and dyspareunia can be the presenting features and some patients may present with polyserositis, bronchiolitis obliterans, and malabsorption. All of these problems warrant discussion with a transplant team, and all patients undergoing transplantation should have early and consistent oral care to prevent caries with involvement of a dentist.

Most patients with chronic GVHD require therapy with corticosteroids, often in association with tacrolimus(Drug information on tacrolimus) or other medications. Thus, the sequelae of chronic steroid use is an important component of care, including diabetes, lipid abnormalities, increase in blood pressure, skin changes, muscle atrophy, gastritis, pancreatitis, and psychological effects. Unlike acute GVHD, organ injury due to chronic GVHD may be very slow to resolve, necessitating long courses of treatment. In addition, tapering of immunosuppression may result in a flare requiring another course of treatment, so that the ultimate management and resolution of GVHD may occur over years. The most important aspect of care is preventing infection. These patients are especially susceptible to reactivation of CMV, HSV and varicella zoster infection, recurrent sinusitis or bronchitis and pneumocystis infection and require ongoing prevention therapy, as previously described. Although all patients should undergo re-vaccination, patients with chronic GVHD may not respond as well, and particular attention must be paid to these infections. Live vaccines such as measles, mumps and rubella are not administered until two years after hematopoietic cell transplantation in the absence of chronic GVHD and immunosuppressive therapy. Family members should receive routine vaccines, including influenza, and patients should avoid contact with children who received oral polio virus vaccine for about a month after vaccination.

Endocrine dysfunction

Hypothyroidism is common after hematopoietic cell transplantation, occurring in about a quarter of patients, particularly after total body irradiation. Thyroid adenomas and carcinomas may occur at rates higher than expected. In general, adrenal and pituitary function is not affected, although patients on long-term steroids may have secondary hypoadrenalism and may require testing or even replacement therapy in the setting of decreased adrenal reserve.

Gonadal dysfunction is very common after transplantation, especially if the patient received high-dose chemotherapy and radiation. Most men have relatively normal testosterone and luteinizing hormone levels but, when low, should have replacement therapy usually through the use of an androgen patch or testosterone injections. Women typically are anovulatory and have high levels of follicle-stimulating hormone and luteinizing hormone and young women should be on replacement therapy. Infertility is not a universal consequence of transplantation.

Increasingly, osteoporosis is a recognized problem in hematopoietic cell transplantation and often is a process begun even before transplantation, likely due to the direct effect of hematologic cancers as well as their treatment. Thus, all patients require periodic bone density evaluations and adequate attention to either vitamin D and calcium replacement or, in some cases, the use of a bisphosphonate.

Avascular necrosis may occur in up to 5% of patients and is usually related to the use of corticosteroids and radiation. The hips are the most commonly affected, but ankles and shoulders have also been involved and successful joint replacement has been performed.