Sarcopenic obesity derived from PET/CT predicts mortality in lymphoma patients undergoing hematopoietic stem cell transplantation.

BACKGROUND: Sarcopenic Obesity (SO) is associated with worse survival among chemotherapy recipients. Research on SO is scarce among lymphoma patients receiving Hematopoietic Stem Cell Transplantation (HSCT). AIM: assess prevalence of SO pre-HSCT (T0) and 3 months post-HSCT (T1) in lymphoma patients and determine the power of SO at T0 and T1 in predicting survival. METHODS: Consecutive patients (age ≥16 years) having B and T cell lymphoma who underwent SCT and who had PET/CT scan pre-SCT and 3 months post SCT were included in the study. A cross sectional image was analyzed at the level of the 3rd Lumber Vertebrae to assess body composition parameters. RESULTS: 93 patients [mean age: 38 (range: 17-70 years), 52 (55.9%) males, 45 (48%) Hodgkin and 48 (52%) Non-Hodgkin lymphoma, 81 (87%) autologous and 12 (13%) allogeneic SCT)] met the inclusion criteria. From T0 to T1, Sarcopenia rates increased (27% at T0 to 38% at T1, p = 0.013), Visceral adiposity decreased (46% at T0 to 30% at T1, p = 0.03) and SO decreased (42% at T0 to 20% at T1, p < 0.01). Length of stay, overall survival and progression free survival were significantly better in patients without sarcopenic obesity at T1. Cox-regression revealed SO at T1 was a risk factor for mortality [Adjusted Hazards Ratio = 8.2 (95% Confidence Interval: 1.9-36.2)]. CONCLUSION: Sarcopenic obesity, prevalent in 42% of patients pre-HSCT, decreased 3 months post HSCT as lymphoma patients lost skeletal muscle and visceral adipose tissues. SO at T1 was the most impactful risk factor for mortality.

Corrigendum: Disease status is a more reliable predictive factor than histology in lymphoma patients after reduced-intensity conditioning regimen and allo-SCT.

This corrects the article DOI: 10.1038/bmt.2012.225.

Progressive multifocal leukoencephalopathy in patients receiving rituximab and cyclophosphamide after haplo-identical T-cell replete transplantation and review of the literature.

John Cunningham virus (JCV) reactivation, occurring mainly in immunocompromised patients, leads to progressive multifocal leukoencephalopathy, an uncommon but lethal disease. JCV reactivation after T-cell replete haploidentical stem cell transplantation, in the pre-cyclophosphamide era, is poorly represented in the literature. We therefore describe two cases of acute myeloid leukemia who developed JCV reactivation after receiving cyclophosphamide and rituximab post haploidentical stem cell transplantation, and review the literature, aiming to a better understanding of the disease course and its risk factors.

Haploidentical transplantation with post-infusion cyclophosphamide in advanced Hodgkin lymphoma.

We investigated the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of advanced Hodgkin lymphoma (HL). Sixty-two consecutive HL patients underwent haplo-HSCT. Unmanipulated stem cells and post-transplant cyclophosphamide were given to all patients as GVHD prophylaxis. At 100 days, the cumulative incidence of grades 2-3 and grades 3-4 acute GVHD was 23% and 4%, respectively. The chronic GVHD (cGVHD) cumulative incidence was 16%, with one patient experiencing severe cGVHD. The 3-year OS, PFS, relapse rates and 1-year non-relapse mortality (NRM) were 63%, 59%, 21% and 20%, respectively. Uncontrolled disease status and high hematopoietic cell transplantation comorbidity index (HCT-CI) were associated with lower OS, whereas PBSC was an independent protective factor. Uncontrolled disease and HCT-CI >2 was predictive for NRM. Finally, disease status other than CR was predictive of relapse. In conclusion, haplo-HSCT is a valid treatment in advanced HL, offering excellent rates of survival and acceptable toxicities.

Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT.

Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.

Inhibition of FLT3 in AML: a focus on sorafenib.

FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma. Sorafenib monotherapy or in combination with conventional chemotherapy, has been evaluated in various settings in AML, including front-line, relapsed or refractory disease including post-allograft failures and, more recently, as post-transplant maintenance therapy. Encouraging data have emerged with several other agents like lestaurtinib, midostaurin, crenolanib, gilteritinib and quizartinib. Although transient responses to FLT3 inhibitors are often observed in case of disease relapse, the most promising approach is the use of FLT3 inhibitors either in combination with induction chemotherapy or as consolidation/maintenance therapy after allogeneic hematopoietic cell transplantation. In this review, we summarize the clinical data on sorafenib and other FLT3 inhibitors in AML.

Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party.

We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: (1) allo-HSCT upfront (n=1924), (2) tandem auto-allo-HSCT (n=2004) and (3) allo-HSCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allo-HSCT over the years. Upfront allo-HSCT use increased up to year 2000, followed by a decrease thereafter and represented 12% of allo-HSCTs performed in 2012. Tandem auto-allo-HSCT peaked around year 2004 and contributed to 19% of allo-HSCTs in 2012. Allo-HSCT as salvage after one or two or three autografts was steadily increasing over the last years and represented 69% of allo-HSCTs in 2012. Remarkable heterogeneity in using allo-HSCT was observed among the different European countries. The 5-year survival probabilities from time of allo-HSCT for the three groups after year 2004 were 42%, 54% and 32%, respectively. These results show that the use of allo-HSCT is increasing in Europe, especially as second line treatment and beyond. There is an unmet need for well-designed prospective studies investigating allo-HSCT as salvage therapy for MM.

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes.

Unmanipulated haploidentical transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy) represents an alternative for patients with high-risk diseases lacking HLA-identical donor. Although it provides low incidences of GVHD, the efficacy of Haplo-SCT is still questioned, especially for patients with myeloid malignancies. Thus, we analyzed 60 consecutive patients with refractory (n=30) or high-risk CR (n=30) AML or myelodysplastic syndromes (MDSs) who underwent PT-Cy Haplo-SCT. The median age was 57 years (22-73 years), hematopoietic cell transplantation comorbidity index was ⩾3 in 38 patients (63%) and Haplo-SCT was the second allogeneic transplantation for 10 patients (17%). Although most of patients received PBSC as graft source (n=48, 80%), we found low incidences of grade 3-4 acute (2%) and severe chronic GVHD (4%). Among patients with high-risk CR diseases, 1-year non-relapse mortality, cumulative incidence of relapse, progression-free and overall survivals were 20%, 32%, 47% and 62%, respectively. In patients with refractory disease, corresponding results were 34%, 35%, 32% and 37%, respectively. We conclude that PT-Cy Haplo-SCT could provide promising anti-leukemic effect even in the setting of very advanced diseases. Thus, it represents a viable alternative for high-risk AML/MDS patients without HLA-identical donor.

Nonmyeloablative conditioning, unmanipulated haploidentical SCT and post-infusion CY for advanced lymphomas.

Allo-SCT is regularly performed in advanced lymphoma. Haploidentical family donors are a valuable source of hematopoietic stem cells and transplants from these donors, using T-repleted grafts, has recently been successfully reported. We report on 49 patients with refractory lymphoma who received T-repleted haploidentical SCT with a non-myeloablative regimen and post-transplant CY. The median time to recover ANC >0.5 × 10e9/L and transfusion independent plt count >20 × 10e9/L was 20 days (range 14-38) and 26 days (range 14-395). The probability to reach ANC >0.5 × 10e9/L at 30 days was 87% and transfusion independent plt count >20 × 10e9/L at 100 days was 87%. The cumulative incidence of grade 2-4 acute GVHD (aGVHD) was 25.6% (95% confidence interval (CI): 12.9-38.3%) and the cumulative incidence of chronic GVHD (cGVHD) was 5.2% (95% CI: 0-12.4%). The median follow-up is 20.6 months (range 12-54), and the projected 2-year OS and PFS were 71 and 63%. The relapse rate was 18.7% (95% CI: 7.6-29.8%) and the median time to relapse was 4.4 months (range 1.1-8.3). At 2 years, cumulative incidence of NRM was 16.3% (95% CI: 5.9-26.8%). T-repleted Haploidentical transplantation with post-infusion CY is a feasible and effective therapy in the poor prognosis of advanced lymphoma patients.