Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease.

BACKGROUND: The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival. METHODS: 144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma. 'Full donor chimerism' was defined as ≥99% donor cells and three patient groups were defined: 40% with full donor chimerism (FC) in both PBMC and T-cells; 25% with mixed chimerism (MC) within both compartments and 35% with 'split' chimerism (SC) characterised by full donor chimerism within PBMC and mixed chimerism within T-cells. RESULTS: In patients with myeloid disease a pattern of mixed chimerism (MC) was associated with a one year relapse rate of 45% and a five year overall survival of 40% compared to values of 8% and 75%, and 17% and 60%, for those with SC or FC respectively. The pattern of chimerism had no impact on clinical outcome for lymphoma. CONCLUSION: The pattern of lineage-specific chimerism at 50 days after transplantation is highly predictive of clinical outcome for patients with myeloid malignancy and may help to guide subsequent clinical management.

Reduced-intensity conditioning allogeneic transplantation after salvage treatment with DT-PACE in myeloma patients relapsing early after autologous transplant.

OBJECTIVE: In this retrospective single-centre study, we have looked into the transplant outcomes(overall survival OS, progression-free survival PFS, GvHD) and the role of chimerism, DLI and pretransplant characteristics in patients who had a suboptimal response (<12 months) to an autologous stem cell transplant for myeloma and underwent an alemtuzumab T-cell depleted reduced-intensity allograft(RIC). METHODS: Twenty-four patients were salvaged with two cycles of DT-PACE and received a RIC transplant with fludarabine, melphalan and alemtuzumab. All the patients received PBSC grafts, eight patients had a sibling donor, and 16 had a graft from a fully matched unrelated donor. The median follow-up was 65.3 months (6-132 months). RESULTS: The median overall survival was 55.4 months. DLI administration was associated with a trend towards better overall survival (P=.05). Disease status at allo-HCT, PR or VGPR, ISS score and CMV serostatus was not significant predictors of OS and PFS. Full donor whole blood chimerism (≥98%) at 3 months post-transplant was associated with PFS (P=.04) but did not have a significant impact on OS(P=.45). CONCLUSION: Reduced-intensity alemtuzumab-conditioned allograft for myeloma after DT-PACE salvage chemotherapy is an efficient and low toxicity treatment for those who had a suboptimal response postautologous stem cell transplant for myeloma.

Allogeneic transplant outcomes are not affected by body mass index (BMI) in patients with haematological malignancies.

Bone marrow transplantation is frequently used as a consolidation therapy in patients with haematological malignancies to improve the outcome of these patients. Obese individuals have larger absolute lean body and fat masses than non-obese individuals of the same age, gender and height, which might lead to altered pharmacokinetics of chemotherapeutic agents. Data on the impact of body mass on transplant outcome is conflicting. This study included 331 patients (M, 230; F, 101) with 336 allogeneic transplant episodes from two large teaching hospitals in the West Midlands region in United Kingdom. A total of 105 patients had acute myeloid leukaemia, 83 had non-Hodgkin's lymphoma, three had myeloma, 21 had Hodgkin's lymphoma, 34 had acute lymphoblastic leukaemia, 19 had chronic myeloid leukaemia, 22 had chronic lymphocytic leukaemia, 24 had myelodysplasia, seven had T cell non-Hodgkin's lymphoma, six had aplastic leukaemia and seven had myelofibrosis. At transplantation, 40% (N = 133) of the patients had normal and 60% (N = 198) had high body mass index (BMI) with 14% of the patients being obese (BMI >30). After a median follow-up of 24 months (range, 2-79), the mean overall survival (OS) in patients undergoing allograft with normal BMI was 31 months as compared to 39 with high BMI (p:0.06). The mean progression free survival (PFS) in patients undergoing allograft with normal BMI was 33 months as compared to 38 with high BMI (p = 0.13). Of the patients in the high and obese BMI group, 16% developed acute GvHD with 8% grade III-IV and 28% in the normal BMI group with 14% grade III-IV acute GvHD (p = 0.11). Of the patients in the high BMI group, 17% developed chronic GvHD and 30% of the patients in the normal BMI group (p = 0.09). However, higher infection rates and more days of inpatient stay in the first year post-transplant were observed in the high BMI and obese patients, but there was no difference in ITU admissions. This study shows that high BMI and obesity does not adversely impact on either OS or PFS in patients undergoing allogeneic transplantation for haematological malignancies, but it does have a significant impact on infection rates and hospitalisation of high BMI and obese patients. We recommend that patients with high BMI should not be excluded from allogeneic transplantation; however, good supportive care and careful patient selection on the basis of comorbidity index should be undertaken in order to avoid the risks from the increased rates of infection.

Performing bone marrow harvest on an outpatient basis: a single center UK experience.

Bone marrow harvest (BMH) has historically been performed on an inpatient basis with a minimum of overnight inpatient stays. We commenced a program of outpatient (day case) BMH in 1999, performing 54 day case BMHs over a 3-year period. Of the total of 54 cases, 51 were known patients with hematological malignancies and 3 were healthy normal donors. Seven were excluded from day case BMH. Five (10.6%) of 47 patients/donors who were accepted for day case BMH required overnight admission. Two developed hypotension requiring intravenous fluid resuscitation. Two had excessive vomiting and 1 a difficult and prolonged harvest and was admitted at the request of the anesthetist. None of the patients admitted required more than overnight admission and 42 (89.4%) were discharged the same evening. In conclusion, day case BMH is safe, cost-effective, and reduces the pressure on inpatient beds.