Mobilization failure is an important issue in stem cell transplantations. Stem cells are yielded from the peripheral blood via apheresis. Granulocyte colony-stimulating factor (G-CSF) is the most ...commonly used mobilization agent among patients and donors. G-CSF is administered subcutaneously for multiple days. However, patients with mobilization failure cannot receive autologous stem cell transplantation and, therefore, cannot be treated adequately. The incidence rate of mobilization failure among patients is about 6-23%. Plerixafor is a molecule that inhibits the binding of chemokine receptor-4 with stromal-cell-derived factor-1, thereby resulting in the release of CD34+ cells in the peripheral blood. Currently, plerixafor is used in patients with mobilization failure with G-CSF and is administered subcutaneously. Several studies conducted on different clinical settings have shown that plerixafor is effective and well tolerated by patients. However, more studies should be conducted to explore the optimal approach for plerixafor in patients with mobilization failure. The incidence of mobilization failure among donors is lower. However, plerixafor is not approved among donors with mobilization failure. Moreover, several clinical studies in donors have shown a beneficial effect of plerixafor. In addition, the adverse events of plerixafor are mild and transient, which can overcome the adverse events due to G-CSF. This review assessed the current role and effects of plerixafor in stem cell mobilization for autologous and allogeneic stem cell transplantations. Keywords: stem cell mobilization, apheresis, autologous stem cell transplantation, allogeneic stem cell transplantation
PURPOSE OF REVIEWNowadays, plerixafor is approved for patients who fail to mobilize sufficient CD34 cells for an autologous stem cell transplantation. Plerixafor is effective in the majority of these ...patients, who otherwise could not be treated adequately. We discussed in this review the current status of the optimal use of plerixafor in different clinical diagnoses and settings.
RECENT FINDINGSPlerixafor seems to be more effective in patients with multiple myeloma than in lymphoma. Even patients who had very low circulating CD34 cells before administration of plerixafor have an important benefit. Several strategies in different clinical settings showed an effective response after administration of plerixafor, without the superiority of one strategy. Plerixafor is well tolerated with acceptable toxicity; however, it is an expensive drug.
SUMMARYPlerixafor is an effective drug in patients who fail to mobilize with conventional strategy. No strategy seems superior for the optimal use of plerixafor. More studies focusing on the kinetics and cost-effectiveness are needed.
Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail ...patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex).
Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years.
The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles.
Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that ...doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages.
We assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses.
After a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m
had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m
doxorubicin (
= .004). The risk increase associated with doxorubicin (yes
no) was not modified by age at first treatment (hazard ratio HR
, 1.5 95% CI, 0.9 to 2.6; HR
, 1.3 95% CI, 0.9 to 1.9) or chest RT (HR
, 1.9 95% CI, 1.06 to 3.3; HR
, 1.2 95% CI, 0.8 to 1.8).
This study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.
Patients with MYC rearranged (MYC-R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Previously, we demonstrated in a single-arm phase II trial (HOVON-130) that addition of lenalidomide ...to R-CHOP (R2CHOP) is well-tolerated and yields similar complete metabolic remission rates as more intensive chemotherapy regimens in literature. In parallel with this single-arm interventional trial, a prospective observational screening cohort (HOVON-900) was open in which we identified all newly diagnosed MYC-R DLBCL patients in the Netherlands. Eligible patients from the observational cohort that were not included in the interventional trial served as control group in the present risk-adjusted comparison. R2CHOP treated patients from the interventional trial (n = 77) were younger than patients in the R-CHOP control cohort (n = 56) (median age 63 versus 70 years, p = 0.018) and they were more likely to have a lower WHO performance score (p = 0.013). We adjusted for differences at baseline using 1:1 matching, multivariable analysis, and weighting using the propensity score to reduce treatment-selection bias. These analyses consistently showed improved outcome after R2CHOP with HRs of 0.53, 0.51, and 0.59, respectively, for OS, and 0.53, 0.59, and 0.60 for PFS. Thus, this non-randomized risk-adjusted comparison supports R2CHOP as an additional treatment option for MYC-R DLBCL patients.
Summary
Patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study ...evaluated treatment with R‐PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio‐immunotherapy consolidation with 90Y‐ibritumomab tiuxetan in responsive patients. Primary endpoints were failure‐free survival (FFS) and incidence of grade ≥3 adverse events from start of 90Y‐ibritumomab tiuxetan. The overall response rate after R‐PECC was 50%. Twenty‐nine of 31 responsive patients proceeded to 90Y‐ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after 90Y‐ibritumomab tiuxetan. One‐year FFS and overall survival (OS) from start of 90Y‐ibritumomab tiuxetan was 52% (95% confidence interval CI, 33–68%) and 62% (95% CI, 42–77%), respectively. One‐year FFS and OS from start of R‐PECC was 28% (95% CI, 17–39%) and 49% (95% CI, 36–61%), respectively. Toxicities of R‐PECC and 90Y‐ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R‐PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with 90Y‐ibritumomab tiuxetan resulted in long‐term response durations in approximately one third of the patients that received it.
BACKGROUND: Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell (RBC) transfusions. Whether platelet (PLT) and/or plasma ...transfusions are a marker for more concomitant RBC transfusions or are independently associated with complications after cardiac surgery is unknown.
STUDY DESIGN AND METHODS: Data from two randomized controlled studies were combined to analyze the effects of PLT and/or plasma transfusions on postoperative infections, length of stay in the intensive care unit (ICU), all‐cause mortality, and mortality in the presence or absence of infections in the postoperative period.
RESULTS: After adjusting for confounding factors, plasma units and not RBC transfusions were associated with all‐cause mortality. White blood cell (WBC)‐containing RBC transfusions and PLT transfusions were associated with mortality occurring in the presence of or after infections. The number of (WBC‐containing) RBC transfusions was also significantly associated with postoperative infections and with ICU stay for 4 or more days.
CONCLUSION: Although it is difficult to separate the effects of blood components, we found that in cardiac surgery, perioperative plasma transfusions are independently associated with all‐cause mortality. WBC‐containing RBC transfusions and PLT transfusions are independently associated with mortality in the presence of infections in the postoperative period. Future transfusion studies in cardiac surgery should concomitantly consider the possible adverse effects of all the various transfused blood components.
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