Post Stem Cell Transplantation Therapy

Post-stem cell transplantation patients do not require any chemotherapy with the exception of certain patients with lymphoma, who may require localized radiotherapy to the primary site. Because the relapse rate is about 50%, a number of investigators have considered the following post-transplant therapy:

1. Use of double autologous HSCT to eradicate the few remaining logs of tumor cells. Sufficient stem cells can be cryopreserved from a single harvest for two transplants. Non-cross-resistant regimens, each with activity, if not causing considerable toxicity, would be advantageous.

2. Use of cytokines to enhance hematopoietic (shortening the period of neutrope-nia) and immunologic recovery. Cytokines are also used for their antitumor effects, which include the following:

a. Stimulation of host antitumor effector cells b. Direct cytotoxic effect c. Cytostatic effect on tumor cells d. Interference with nutrient and oxygen supply to tumor by acting on tumor vasculature.

3. Use of differentiation inducers (e.g., 13-cis-retinoic acid). These agents can arrest cell proliferation and induce terminal differentiation and may prove

*These approaches are limited by the risk of fatal intracerebral and pulmonary bleeding. Heparin has little effect on the overall incidence of VOD but may reduce the severity of the clinical illness. A dose of 100 units/kg/day of heparin has been shown to be safe.

Table 25-21. Late Sequelae of Allogeneic Stem Cell Transplantation in Children

1. Chronic GVHD

2. Multiple endocrine disorders (hypothyroidism, delayed pubescence, gonadal failure, growth hormone deficiency)"

3. Second malignancies (incidence of 0.6 per 100 person-years)6

4. Sterility due to gonadal failure

5. Cataracts (secondary to radiation therapy); 20-50% incidence at 5-6 years

6. Renal insufficiency (nephrotoxic antibiotics and cyclosporine)

7. Obstructive and restrictive pulmonary disease (occurs in 10-15% of patients with chronic GVHD)

8. Cardiomyopathy

9. Aseptic necrosis of bone

10. Leukoencephalopathy (especially with IT MTX)

11. Immunologic dysfunction

12. Post-transplant lymphoproliferative disorders (PTLD) (occasionally seen in T-cell-depleted stem cell graft recipients)

13. Disturbance in dental development (from TBI) particularly if HSCT takes place in patients less than 6 years of age

Note:The frequency and severity of these sequelae vary considerably with the conditioning required preceding SCT.

"Associated with the use of TBI.

6At 15 years after HSCT, 6% develop second malignancies if not prepared with TBI and 20% for those prepared with TBI regimens.

effective against minimal disease after autologous HSCT. They do not have hematopoietic toxicity and should be well tolerated in autologous HSCT.

4. Use of antimyeloid monoclonal antibody in myeloid leukemia such as gemtuzumab ozogamicin (Mylotarg).

5. Use of low-dose cyclosporine to induce GVHD, which also has a beneficial effect on graft versus leukemia reaction and thus might reduce the relapse rate.

6. For treatment of post-transplant lymphoproliferative disorder, see Chapter 13.

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