Non-ablative transplants can reduce early transplant related toxicity while maintaining the anti-tumor effect associated with complete donor chimerism. These procedures have been undertaken primarily in matched related donor transplants (MRD) with peripheral blood stem cells as opposed to bone marrow. While the increased number of CD34 cells in such products can foster early and more complete engraftment, PBSC have been associated with greater risks of chronic GVHD in fully ablative transplants. Based on our previous data identifying a lower risk of GVHD and comparable engraftment for ablative MRD receiving G-CSF stimulated marrow as compared to PBSC (Serody, BBMT, July,2000), we have undertaken a study (UNC LCCC 9919) evaluating the use of mobilized marrow in non-ablative transplants. The goals were to achieve full donor chimerism and low rates of GVHD. Pts underwent conditioning with FL, 30 mg/m2/d x 5 plus CY, 50 mg/kg/d x 3 followed by 18-20 cc/kg recipient body weight of G-CSF stimulated marrow from a MRD, and MTX on days +1, +3, and +6. Tacrolimus was given from day -1 to day 60 and tapered in the event of disease progression w/o GVHD, or incomplete chimerism. G-CSF was begun on day + 6 to ANC > 1000 x 3. 8 pts (7 MRD, 1 MUD) have been enrolled on the trail to date. All pts had advanced hematologic malignancies (4 NHL, 2 CML, 1 HD, 1 transformed CLL) and none were in CR at the time of NAT. Median age was 58, # CD34 and TNC infused were 1.48 x 10 6 and 3.15 x 10 8 respectively, time to ANC > 500 was 16 days, plts >20K was 23 days. 2 pts never had plts below 50K (1 with full donor chimerism and 1 with no donor engraftment) and one pt remains transfusion dependant. 4 pts have had sustained chimerism > 90%; 2 of these remain in sustained CR, 12 and 5 months post NAT, 1 is in 2nd CR at 17 months post transplant after rituximab salvage and one died on day +156 post transplant with TTP, HSV, CMV and grade 3 GVHD. Of the remaining 4 pts, 1 pt with transformed CLL never engrafted > 10% donor cells but is alive and in remission post autologous reconstitution and rituximab therapy. 3 of these 4 pts have died; one on day 88 of progressive HD in the marrow and 30% donor chimerism; 1 MUD transplant received ATG and unstimulated marrow in addition to the other conditioning agents and died on day +43 with acyclovir resistant HSV of the liver, skin, and presumed viral encephalitis: and one on day +18 of CNS aspergillus. One pt had grade 3 acute GVHD of the liver and grade 2 gut GVHD and two pts had grade 2 acute GVHD of the skin. 4 patients are surviving off immunosuppressive drugs between 5 and 17 months post transplant without e/o GVHD. This approach remains promising with a low rate of GVHD but requires additional efforts to reduce early infectious complications nad promote complete donor chimerism.
Full conference title:
43rd American Society of Hematology (ASH) Annual Meeting
- ASH 43rd (2001)