Patients with Richter's transformation of chronic lymphocytic leukemia (CLL) to diffuse large B‐cell lymphoma (DLBCL‐RT) face a dismal prognosis. A 51‐year‐old female patient diagnosed with CLL with ...deletion (17p) in 2009. CLL treatment included chemoimmunotherapy and targeted substances. DLBCL‐RT was diagnosed in November 2016. After receiving an allogeneic hematopoietic stem cell transplantation, she relapsed in September 2019 and tisagenlecleucel was infused in December 2019. Cytokine release syndrome grade 2 was treated with two doses of tocilizumab and the patient was started on 140 mg ibrutinib in February 2020. Our patient remains in remission up to 4 years after CAR T‐cell treatment.
Background
Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal ...mechanism to maintain remission is the induction of the graft‐versus‐tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti‐cancer immune response.
Methods
We designed a phase II clinical trial for patients with relapsed and refractory lymphoid malignancies undergoing aHSCT using a CNI‐free approach consisting of post‐transplant cyclophosphamide (PTCy) and short‐term Everolimus after reduced‐intensity conditioning and matched peripheral blood stem cell transplantation. The results of the 19 planned patients are presented. Primary endpoint is the cumulative incidence and severity of acute GvHD.
Results
Overall incidence of acute GvHD was 53% with no grade III or IV. Cumulative incidence of NRM at 1, 2, and 4 years was 11%, 11%, and 16%, respectively, with a median follow‐up of 43 months. Cumulative incidence of relapse was 32%, 32%, and 42% at 1, 2, and 4 years after transplant, respectively. Four out of six early relapses were multiple myeloma patients. Overall survival was 79%, 74%, and 62% at 1, 2, and 4 years. GvHD‐relapse‐free‐survival was 47% after 3 years.
Conclusions
Using PTCy and short‐term Everolimus is safe with low rates of aGvHD and no severe aGvHD or cGvHD translating into a low rate of non‐relapse mortality. Our results in this difficult to treat patient population are encouraging and warrant further studies.
Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34
hematopoietic stem and progenitor ...cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 10
CD34
cells kg
within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12-201.33, P < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36-549.35, P < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34
HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov , NCT03246529.
To report a case of bilateral diffuse uveal melanocytic proliferation over 30 months follow-up.
Multimodal imaging including ultra-wide-field color fundus photography, blue light fundus ...autofluorescence, swept-source optical coherence tomography, fluorescein angiography, and indocyanine green angiography.
A 49-year-old woman presented with decreased vision 2 months after bladder cancer surgery. Exudative retinal detachment and leopard spot pattern chorioretinopathy were observed in the right eye. Chemotherapy and cystectomy were initiated. Progressive bilateral vision loss occurred with melanocytic proliferation, choroidal thickening, subretinal fibrosis, fluid extravasation, rapid development of mature cataract, multiple iris cysts, and rubeosis, despite plasmapheresis and IV immunoglobulins. After cataract surgery, massive fibrin reaction resulted in a ciliolenticular block. One year later, positron emission tomography-computed tomography revealed absence of metastases. At Month 23, choroidal thickness increased in line with tumor progression. Palliative systemic therapy was initiated. Secondary macular neovascularization was treated with intravitreal antivascular endothelial growth factor injections. Visual acuity was light perception in the right eye and 20/200 in the left eye at last follow-up.
Bilateral diffuse uveal melanocytic proliferation results in progressive melanocyte proliferation and exudation, leading to severe visual loss. In our case, visual acuity was preserved at a low level in one eye under continuous systemic treatment. Systemic corticosteroids are recommended for cataract surgery in the setting of bilateral diffuse uveal melanocytic proliferation to prevent massive fibrin reaction. Intravitreal antivascular endothelial growth factor injections may be indicated if secondary macular neovascularization develops.
Abstract
Background
Immune recovery following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) decisively influences the occurrence of opportunistic infections, one of the leading ...causes of death among this group of patients. Yet, today, there are no laboratory parameters mirroring immune function sufficiently. Torque teno virus (TTV) has already proven itself as a functional immune marker in other settings.
Aims
In this analysis, we investigated whether monitoring of TTV‐DNA load in whole blood is able to provide additional information on the capacity of the immune system to control cytomegalovirus (CMV) replication in allo‐HSCT recipients.
Methods
Whole blood samples from 59 patients were collected upon allo‐HSCT (between Day −7 and +10), on Day +14, +21, +28, +56, +90, and +365 post‐transplant. TTV‐DNA loads and other relevant clinical information were correlated with the risk of CMV infections or reactivations, defined by evidence of viral replication in blood.
Results
CMV serostatus of the recipient and a TTV load below 1000 copies/mL upon allo‐HSCT were significantly associated with an increased incidence of CMV infection or reactivation.
Conclusions
Quantification of TTV load in the early phase of allo‐HSCT procedure could provide additional information in order to identify patients at risk for CMV infection or reactivation.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment option for several hematological diseases. However, the first year post-transplantation is often complicated ...by infections and graft-versus-host disease (GVHD). Improvements in immunological monitoring could reduce such post-transplant complications. Torque Teno virus (TTV), a chronically persisting DNA virus, is reported to be a marker for immune function in immunocompromised patients. In the present study, the TTV kinetics were analyzed to investigate the potential role of TTV viremia as immune-competence read-out after allo-HSCT. Twenty-three monocentric allo-HSCT recipients were retrospectively tested for TTV-DNA in whole blood at given day post-transplant. Dynamics of TTV viremia was analyzed with respect to episodes of non-TTV viral reactivations (CMV, EBV, and BKPyV), acute GVHD, and recovery of immune cells. Recipients affected by persisting viral infections and/or GVHD during the first 100 days after allo-HSCT showed a significantly higher median TTV load at day +30 than patients with a less complicated clinical course (
p
= 0.005). This was also associated with a total lymphocyte count <5.5E+08 cells/L in this high-risk group (
p
= 0.039). These findings suggest that TTV could represent an additional parameter to identify patients at higher risk for complications in the first 100 days following allo-HSCT. Prospective studies, including the monitoring of lymphocyte subsets, are required to define the potential use of TTV in immunological monitoring after allo-HSCT.
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