ABSTRACT
The management of critically ill patients with haematological malignancy (HM) still shows inter- and intra-regional differences. Our objective in this updated review was to address the evidence supporting the potential treatment options, based on multidisciplinary processes, of critically ill patients with HM. A stepwise approach to the critical care pathway of this patient population from the triage to ICU admission to ICU discharge was chosen to emphasise certain key findings. Our main focus relied on significant issues of decision-making in daily clinical routine. The plethora of studies shifted the pragmatic treatment policy into an evidence-based approach. The transfer of a patient with HM from the haematology ward to the ICU and vice versa should be based on a well-defined clinical care process in which the haematologists and intensivists are in close collaboration and direct communication. A protocolised clinical approach to treat a critically ill patient with HM seems helpful to optimise patient-oriented care and patient safety.
Subject(s)
Continuity of Patient Care , Critical Care/methods , Hematologic Neoplasms/therapy , Patient Care Team , Critical Illness/therapy , Humans , Intensive Care Units , Interdisciplinary Communication , Triage/methodsABSTRACT
In myelofibrosis, the introduction of reduced-intensity conditioning (RIC) preceding allogeneic stem cell transplantation (SCT) resulted in lower transplant-related mortality rates compared with myeloablative conditioning. However, lowering the intensity of conditioning may increase the risk of graft failure in myelofibrosis, although hitherto this has not been indisputably proven. We here report the outcome of 53 patients who underwent allogeneic SCT with different conditioning regimens (RIC and non-myeloablative (NMA)) in three transplantation centers in the Netherlands. The cumulative incidence of graft failure within 60 days after SCT was high (28%), and this was primarily associated with the intensity of the conditioning regimen. Cumulative neutrophil engraftment at 60 days was lower in patients who received NMA conditioning compared with those who received RIC (56% vs 84%, P=0.03). Furthermore, of six patients who received a second transplantation after graft failure, the three patients with RIC regimens subsequently engrafted, whereas the three patients who received a second NMA regimen did not. This study indicates that in myelofibrosis, NMA regimens result in high engraftment failure rates. We propose the use of more intensive conditioning regimens, incorporating busulfan or melphalan.
Subject(s)
Cord Blood Stem Cell Transplantation , Graft Survival , Myeloablative Agonists/therapeutic use , Peripheral Blood Stem Cell Transplantation , Primary Myelofibrosis/therapy , Transplantation Conditioning/methods , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Busulfan/therapeutic use , Calreticulin/genetics , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Disease Progression , Female , Humans , Janus Kinase 2/genetics , Male , Melphalan/therapeutic use , Middle Aged , Neutrophils/transplantation , Polycythemia Vera/complications , Primary Myelofibrosis/drug therapy , Primary Myelofibrosis/etiology , Primary Myelofibrosis/genetics , Receptors, Thrombopoietin/genetics , Retrospective Studies , Thrombocythemia, Essential/complications , Treatment Outcome , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use , Whole-Body Irradiation , Young AdultABSTRACT
We performed a prospective phase II study to evaluate clinical safety and outcome in 48 patients with steroid-refractory grade II-IV acute graft-versus-host disease (aGVHD) treated with mesenchymal stromal cells (MSCs). Clinical outcomes were correlated to comprehensive analyses of soluble and cellular biomarkers. Complete resolution (CR) of aGVHD at day 28 (CR-28) occurred in 12 (25%) patients, CR lasting >1 month (CR-B) occurred in 24 (50%) patients. One-year overall survival was significantly improved in CR-28 (75 versus 33%, P=0.020) and CR-B (79 versus 8%, P<0.001) versus non-CR patients. A six soluble biomarker-panel was predictive for mortality (HR 2.924; CI 1.485-5.758) when measured before MSC-administration. Suppression of tumorigenicity 2 (ST2) was only predictive for mortality 2 weeks after but not before MSC-administration (HR 2.389; CI 1.144-4.989). In addition, an increase in immature myeloid dendritic cells associated with decreased mortality (HR 0.554, CI 0.389-0.790). Patients had persisting T-cell responses against defined virus- and leukemia-associated antigens. In conclusion, our data emphasize the need to carefully assess biomarkers in cohorts with homogeneous GVHD treatments. Biomarkers might become an additional valuable component of composite end points for the rapid and efficient testing of novel compounds to decrease lifecycle of clinical testing and improve the success rate of phase II/III trials.
