Low incidence of severe cGvHD and late NRM in a phase II trial of thymoglobulin, tacrolimus and sirolimus for GvHD prevention.

Chronic GvHD (cGvHD) is the leading cause of late non-relapse mortality (NRM) and morbidity after allogeneic hematopoietic stem cell transplant (AHSCT). We analyzed the late effects of a phase II trial testing the efficacy of intermediate dose rabbit anti-thymocyte globulin (Thymoglobulin Thymo) in combination with tacrolimus and sirolimus (TTS) in 47 patients (pts) for the prevention of acute and chronic GvHD after unrelated AHSCT. The median follow-up was 45.2 months. The cumulative incidence of NIH severe cGvHD at 48 months was 6.4% with no new occurrences past 6 months for the entire follow-up period. The overall cumulative incidence of cGvHD was 44.7%. Out of 20 pts who are alive and disease-free at the last follow-up, only 4 pts continue to need systemic immune suppression. We observed low late NRM with only 3 transplant-related deaths after 6 months post transplant. At 4 years of follow-up, the overall cumulative incidence of NRM and disease relapse was 27.7% and 30.0%, respectively. PFS and overall survival (OS) at 4 years were 42 and 47%. At long term follow-up, TTS was associated with low incidence of severe cGvHD and late NRM.

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort.

Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10(6)/L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30⩽400 × 10(6)/L was associated with worse OS, increased NRM and severe aGVHD.

Long-term follow up of patients proceeding to transplant using plerixafor mobilized stem cells and incidence of secondary myelodysplastic syndrome/AML.

We report the long-term follow up of 49 patients (pts) enrolled on plerixafor compassionate use protocol. Thirty-seven pts (76%) had failed one previous mobilization attempt, while 12 (24%) had failed two or more previous attempts. Using the combination of plerixafor and granulocyte colony-stimulating factor, we collected2.5 × 10(6) CD34+cells/kg in 33 pts (67%). Forty-three of the 49 pts proceeded to an auto-SCT (ASCT). The median days to WBC and platelet engraftment were 11 (range, 9-13 days) and 16 (range, 11-77 days) days post ASCT, respectively. The median WBC count, Hb and platelet counts 1 year after ASCT were 4.7 × 10(9)/L, 12.2 g/dL and 109 × 10(9)/L, respectively. With median follow up of 42 months (range <1-54 months), 21 pts had evidence of disease progression. Five pts developed myelodysplastic syndrome (MDS)/AML at median of 29 months post ASCT. The cumulative incidence of MDS/AML at 42 months was 17% (95% confidence interval, 6 to 32%). Development of secondary MDS/AML in pts proceeding to ASCT after plerixafor mobilization needs to be studied further in a larger cohort.

Large pericardial effusion as a complication in adults undergoing SCT.

Large pericardial effusion (LPE) leading to cardiac tamponade is a rare complication described in patients undergoing SCT. This complication is considered to be a manifestation of chronic GVHD; however its pathophysiology is poorly understood. Currently, there are no published data systematically describing the incidence, clinical characteristics and outcomes of LPEs in adult stem cell transplant recipients. We retrospectively evaluated 858 adult patients (512 autologous, 148 related and 198 unrelated donor) who underwent hematopoietic stem cell and BM transplants at our institution from 2005 to 2008 for the development of post transplant LPE. Seven patients (0.8%) were found to have LPEs and all these patients had undergone unrelated allografts. The median day of diagnosis post transplant was 229 (range 42-525). None of these patients had active manifestations of GVHD other than serositis at the time of LPE detection. Pericardial window (PW) was successfully placed in all patients who developed cardiac tamponade and most patients with LPE were effectively treated by increasing immunosuppression. We conclude that LPE is a rare late complication after allogeneic transplant in adults and in our study developed only after unrelated transplant. PW can be safely performed in these patients and LPEs can be successfully treated with intensification of systemic immunosupression.

Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies.

In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.