Peripheral-blood autologous stem-cell transplantation (ASCT) in patients with HIV-related lymphoma (HIV-Ly) has been reported as a safe and useful procedure. Herein we report the European Group for ...Blood and Marrow Transplantation experience on patients with HIV-Ly undergoing ASCT.
This was a retrospective, multicentric, registry-based analysis.
Since 1999, 68 patients from 20 institutions (median age, 41 years; range, 29 to 62 years) were included, diagnosed with non-Hodgkin's lymphoma (NHL; n = 50) or Hodgkin's lymphoma (n = 18). At the time of ASCT, 16 patients were in first complete remission (CR1); 44 patients were in CR more than 1, partial remission, or chemotherapy-sensitive relapse (chemo-S); and eight patients had chemotherapy-resistant disease. The median number of CD34(+) cells infused was 4.5 x 10(6)/kg (range, 1.6 to 21.2 x 10(6)/kg). Median time to neutrophil and platelet engraftment were 11 days (range, 8 to 36 days) and 14 days (range, 6 to 455 days), respectively, with a cumulative incidence (CI) at 1 year of 95.6% and 87%, respectively. CI of nonrelapse mortality (NRM) was 7.5% at 12 months after ASCT, mainly because of bacterial infections. CI of relapse was 30.4% at 24 months, statistically related with not being in CR at ASCT (relative risk RR = 3.6), NHL histology other than diffuse large B-cell lymphoma (RR = 3.4), and use of more than two previous treatment lines (RR = 3). At a median follow-up of 32 months (range, 2 to 81 months), progression-free survival (PFS) was 56%. Patients not in CR or with refractory disease at ASCT had poorer PFS (RR = 2.4 and 4.8, respectively).
Similarly to HIV-negative patients with lymphoma, ASCT is a useful treatment for patients with HIV-Ly and is associated with low NRM, mainly when performed in early stages and chemo-S disease.
The burden and timeline of posttransplant infections are not comprehensively documented in the current era of immunosuppression and prophylaxis.
In this prospective study nested within the Swiss ...Transplant Cohort Study (STCS), all clinically relevant infections were identified by transplant-infectious diseases physicians in persons receiving solid organ transplant (SOT) between May 2008 and December 2014 with ≥12 months of follow-up.
Among 3541 SOT recipients, 2761 (1612 kidney, 577 liver, 286 lung, 213 heart, and 73 kidney-pancreas) had ≥12 months of follow-up; 1520 patients (55%) suffered 3520 infections during the first year posttransplantation. Burden and timelines of clinically relevant infections differed between transplantations. Bacteria were responsible for 2202 infections (63%) prevailing throughout the year, with a predominance of Enterobacteriaceae (54%) as urinary pathogens in heart, lung, and kidney transplant recipients, and as digestive tract pathogens in liver transplant recipients. Enterococcus spp (20%) occurred as urinary tract pathogens in kidney transplant recipients and as digestive tract pathogens in liver transplant recipients, and Pseudomonas aeruginosa (9%) in lung transplant recipients. Among 1039 viral infections, herpesviruses predominated (51%) in kidney, liver, and heart transplant recipients. Among 263 fungal infections, Candida spp (60%) prevailed as digestive tract pathogens in liver transplant recipients. Opportunistic pathogens, including Aspergillus fumigatus (1.4%) and cytomegalovirus (6%), were rare, scattering over 12 months across all SOT recipients.
In the current era of immunosuppression and prophylaxis, SOT recipients experience a high burden of infections throughout the first year posttransplantation, with rare opportunistic pathogens and a predominance of bacteria.
The development of tyrosine‐kinase inhibitors (TKIs) has improved survival of patients with chronic myeloid leukemia (CML). Some patients may become resistant to TKIs and require hematopoietic stem ...cell transplant (HSCT) that is highly gonadotoxic. Fertility preservation with ovarian stimulation might be indicated but is challenging if patients need to remain on TKIs until HSCT because TKIs may compromise follicular development and response to ovarian stimulation. We report the case of a patient with CML resistant to TKI and planned for an HSCT, in which treatment by TKI was replaced by interferon‐α before and during ovarian stimulation for fertility preservation. Successful ovarian stimulation was performed, allowing cryopreservation of nine zygotes. Hematopoietic stem cell transplantation was performed, and at present, 3 years later, the patient presents a sustained major molecular response.
A case of a patient with chronic myeloid leukemia resistant to tyrosine‐kinase inhibitors is reported.
Abstract
Background
BNT162b2 by Pfizer-BioNTech and mRNA-1273 by Moderna are the most commonly used vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. ...Head-to-head comparison of the efficacy of these vaccines in immunocompromised patients is lacking.
Methods
Parallel, 2-arm (allocation 1:1), open-label, noninferiority randomized clinical trial nested into the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study. People living with human immunodeficiency virus (PLWH) or solid organ transplant recipients (SOTR; ie, lung and kidney) from these cohorts were randomized to mRNA-1273 or BNT162b2. The primary endpoint was antibody response to SARS-CoV-2 spike (S1) protein receptor binding domain (Elecsys Anti-SARS-CoV-2 immunoassay, Roche; cutoff ≥0.8 units/mL) 12 weeks after first vaccination (ie, 8 weeks after second vaccination). In addition, antibody response was measured with the Antibody Coronavirus Assay 2 (ABCORA 2).
Results
A total of 430 patients were randomized and 412 were included in the intention-to-treat analysis (341 PLWH and 71 SOTR). The percentage of patients showing an immune response was 92.1% (95% confidence interval CI: 88.4–95.8; 186/202) for mRNA-1273 and 94.3% (95% CI: 91.2–97.4; 198/210) for BNT162b2 (difference: -2.2%; 95% CI: -7.1 to 2.7), fulfilling noninferiority of mRNA-1273. With the ABCORA 2 test, 89.1% had an immune response to mRNA-1273 (95% CI: 84.8–93.4; 180/202) and 89.5% to BNT162b2 (95% CI: 85.4–93.7; 188/210). Based on the Elecsys test, all PLWH had an antibody response (100.0%; 341/341), whereas for SOTR, only 60.6% (95% CI: 49.2–71.9; 43/71) had titers above the cutoff level.
Conclusions
In immunocompromised patients, the antibody response of mRNA-1273 was noninferior to BNT162b2. PLWH had in general an antibody response, whereas a high proportion of SOTR had no antibody response.
This randomized trial confirmed the noninferiority of the severe acute respiratory syndrome coronavirus 2 vaccine mRNA-1273 compared with BNT162b2 in terms of antibody response in immunocompromised patients. Although people with human immunodeficiency virus had a sufficient antibody response, a high proportion of transplant recipients had no antibody response.
The effects of two nitric oxide synthase (NOS) inhibitors with different isoform selectivity were compared in a murine model of endotoxemia. Mice challenged with 70 mg/kg intraperitoneal (ip) ...lipopolysaccharide (LPS) were treated 6 h after LPS with either NG-γ-L-arginine methyl ester (LNAME, nonselective NOS inhibitor, 10–60 mg/kg), L-canavanine (selective inhibitor of inducible NOS, 50–300 mg/kg), or saline (0.2 mL) given ip. In a subset of mice, plasma concentrations of nitrate (NO breakdown product), lipase (pancreas injury), lactate dehydrogenase, and transaminases (liver injury) were measured 16 h after LPS. Although both inhibitors reduced plasma nitrate, they produced contrasting effects on survival and organ injury. L-NAME enhanced liver damage and tended to accelerate the time of death, while L-canavanine significantly reduced mortality and had no deleterious effects in terms of organ damage. These results indicate that nonselective NOS inhibitors are detrimental in endotoxic shock and support the potential usefulness of selective inducible NOS inhibitors in this setting.
Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk ...factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.
HLA-specific memory B cells may contribute to the serum HLA antibody pool upon antigen reexposure. The aim of this pilot study was to investigate the presence of concurrent donor-specific memory B ...cell-derived HLA antibodies (DSA-M) in renal allograft recipients with pretransplant donor-specific HLA antibodies (DSA) and its association with occurrence of antibody-mediated rejection (AMR) using a recently developed method.
Twenty patients with Luminex single antigen bead (SAB) assay-defined DSA but negative complement-dependent cytotoxicity crossmatches were enrolled. Plasma samples and peripheral blood mononuclear cells were collected at 3 timepoints (pretransplant, mo 6, mo 12). We analyzed IgG-purified and concentrated culture supernatants from polyclonally activated peripheral blood mononuclear cells using SAB assays and compared HLA antibody profiles with same day plasma results.
Plasma SAB analysis revealed 35 DSA in 20 patients pretransplant. DSA-M were detected in 9 of 20 (45%) patients and for 10 of 35 specificities (29%). While median mean fluorescence intensity values of DSA with concurrent DSA-M (5877) were higher than those of DSA without DSA-M (1476), 3 of 6 patients with AMR and low mean fluorescence intensity DSA (<3000) had DSA-M. Overall, pretransplant DSA/DSA-Mpos allograft recipients showed a higher incidence of biopsy-proven (sub)clinical AMR (P = 0.032) and a higher extent (g≥1 + ptc≥1) of microvascular inflammation (67% vs 9%, P = 0.02). In 17 patients (28 DSA) with posttransplant analyses, persisting DSA posttransplant had more often DSA-M (6/12; 50%) than nonpersisting DSA (2/16; 13%).
Assessment of DSA-M might be a novel tool to supplement serum HLA antibody analysis for pretransplant risk stratification in patients with DSA.
Background
Pre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in ...kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).
Methods
We investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.
Results
Pre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.
Conclusion
Our results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.
Background
Descriptive data on Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients (SOTr) in the era of routine Pneumocystis‐prophylaxis are lacking.
Methods
All adult SOTr ...between 2008 and 2016 were included. PJP was diagnosed based on consensus guidelines. Early‐onset PJP was defined as PJP within the first‐year‐post‐transplant.
Results
41/2842 SOTr (1.4%) developed PJP (incidence rate: 0.01/1000 person‐days) at a mean of 493‐days post‐transplant: 21 (51.2%) early vs 20 (48.8%) late‐onset PJP. 2465 (86.7%) SOTr received Pneumocystis‐prophylaxis for a mean 316 days. PJP incidence was 0.001% and 0.003% (log‐rank < 0.001) in SOTr with and without Pneumocystis‐prophylaxis, respectively. PJP was an early event in 10/12 (83.3%) SOTr who did not receive Pneumocystis‐prophylaxis and developed PJP, compared to those patients who received prophylaxis (11/29, 37.9%; P‐value: 0.008). Among late‐onset PJP patients, most cases (13/20, 65%) were observed during the 2nd year post‐transplant. Age ≥65 years (OR: 2.4, P‐value: 0.03) and CMV infection during the first 6 months post‐SOT (OR: 2.5, P‐value: 0.006) were significant PJP predictors, while Pneumocystis‐prophylaxis was protective for PJP (OR: 0.3, P‐value: 0.006) in the overall population. Most patients (35, 85.4%) were treated with trimethoprim‐sulfamethoxazole for a mean 20.6 days. 1‐year mortality was 14.6%.
Conclusions
In the Pneumocystis‐prophylaxis‐era, PJP remains a rare post‐transplant complication. Most cases occurred post‐PJP‐prophylaxis‐discontinuation, particularly during the second‐year‐post‐transplant. Additional research may help identify indications for Pneumocystis‐prophylaxis prolongation.
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