Interest of a Third Dose of BNT162b2 Anti- Sars-Cov-2 mRNA Vaccine in Allogeneic Hematopoietic Stem-Cells Recipients

Abstract Introduction In a previous observational study of 117 allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients, we found that 83 % of them achieved a specific humoral response after two doses (V1 and V2) of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine (Pfizer BioNTech). However, although 61.5% of the patients achieved the highest detectable IgG titers, this proportion remained significantly lower than what was observed in healthy controls, where 100% reached these highest antibody titers. Here, we investigated whether a third dose of vaccine would improve the anti- SARS-CoV-2 response in Allo-HSCT recipients. Methods This monocentric retrospective study aimed at evaluating the efficacy of a third vaccine (V3) of BNT162b2 in a cohort of Allo-HSCT adult recipients. Patients with previous clinical or asymptomatic biological COVID-19 infection at V1 were excluded from the study. A cohort of healthy volunteers (caregivers from the Clinical Hematology Department) who had also already received V1 and V2 was considered as controls. All participants were vaccinated between January 20 and June 1, 2021. Analyses were performed in July 2021. Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested after V2 for all subjects (Serology post V2, SpV2) using the Roche Elecsys® assay. All subjects benefited later from another evaluation of specific serum antibodies as monitoring (Serology post V2+, SpV2+) or after V3 (Serology post V3, SpV3). Various serological methods were used for these later assays because performed outside of our hospital for some patients. Considering thresholds of negativity and positivity as well as highest values for each test, we were able nevertheless to distinguish 4 sub-groups: i) negativity at both SpV2 & SpV2+/SpV3, ii) increase of the IgG titer between SpV2 & SpV2+/SpV3, including patients showing seroconversion, iii) decreased or stable IgG titer between SpV2 & SpV2+/SpV3 and iv) highest IgG titers at both SpV2 and SpV2+/SpV3. Results A cohort of 25 controls and 114 patients, including 91 who received V3 (V3+) and 23 who did not (V3-) was considered for the purpose of this study. The characteristics of participants and delays from SpV2 to SpV2+ or SpV2 to SpV3 are reported in Tables 1 and 2. The serological methods used for the latest assays are reported in Table 2 with criteria of negativity, positivity and highest IgG titer values. V3- patients were younger, with less myeloid disease than V3+ cases and had not received myeloablative conditioning. However, both V3+ and V3- groups shared similar median intervals between Allo-HSCT and V1, incidence of previous graft versus host disease (GVHD), proportions of patients under chemotherapy or immunosuppressive drugs and median lymphocyte counts at V1, suggesting similar immune status. The reasons for not receiving V3 were forgetting, refusal or surveillance after detection of the highest IgG titer at SV2. Samples from controls, all evaluated by Roche Elecsys®, showed the highest anti-spike antibody value (>250U/mL) at both SpV2 and SpV2+, suggesting a persistent response without the need of a third vaccine in this healthy population. The proportion of patients still negative at SpV2+/SpV3 was similar between V3- and V3+ patients (17% vs 12%, p=0.74). However, the proportion of patients showing a decreased/stable IgG titer between SpV2 and SpV2+/SpV3 was significantly higher for V3- cases (35% vs 4%, p=0.0001) (Table 2). Moreover, the proportion of patients with the highest IgG titer at SpV2+/SpV3 was significantly higher in the V3+ sub-group (80% vs 43%, p=0.001), even if it remained significantly lower than in controls (p=0.03). The proportion of patients showing an IgG titer increase between SpV2 and SpV2+/SpV3 was higher in V3+ vs V3- patients (24% vs 4%, p=0.06). The difference was not significant as surprisingly one V3- case showed a seroconversion without any argument for SARS-CoV-2 infection between SpV2 and SpV2+. Three patients out of 14 (21%), with a negative SpV2, showed a seroconversion after V3. Finally, with a median follow up from V1 of 106 days in V3+ patients, 138 days in V3- patients and 154 days in controls, no COVID-19 infection was documented in any participant. Conclusion This study shows the interest of a third dose of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine after allograft as more patients are documented with less decrease of IgG titers and the highest IgG values after V3. Figure 1 Figure 1. Disclosures Moreau: Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria.

Download Full-text

Immunosuppressive Compounds Affect the Fungal Growth and Viability of Defined Aspergillus Species

Pathogens ◽

10.3390/pathogens8040273 ◽

2019 ◽

Vol 8 (4) ◽

pp. 273 ◽

Cited By ~ 2

Author(s):

Stanislaw Schmidt ◽

Michael Hogardt ◽

Asuman Demir ◽

Frauke Röger ◽

Thomas Lehrnbecher

Keyword(s):

Fungal Growth ◽

Invasive Fungal Disease ◽

Inhibitory Effect ◽

Immunosuppressive Drugs ◽

Aspergillus Species ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Number Of Patients ◽

Species Specific ◽

The Impact

Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.

Download Full-text

Generation of Epstein Barr Virus Specific Cytotoxic T Lymphocytes (EBVCTLs) Resistant to the Immunosuppressive Drug Tacrolimus (FK506)

Blood ◽

10.1182/blood.v112.11.3536.3536 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3536-3536

Author(s):

Biagio De Angelis ◽

Gianpietro Dotti ◽

Concetta Quintarelli ◽

Leslie E Huye ◽

Lan Zhang ◽

...

Keyword(s):

Immunosuppressive Agents ◽

Retroviral Vector ◽

Immunosuppressive Drugs ◽

Thymidine Uptake ◽

Solid Organ ◽

Cell Transplant ◽

Antigen Specificity ◽

Hematopoietic Stem ◽

Post Transplant

Abstract Adoptive transfer of autologous EBV-CTLs to hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients is a safe and often effective means for prevention and treatment of EBV-associated post transplant lymphoproliferative disorders (PTLD). Although immunosuppressive drugs can be tapered in patients developing PTLD, they often cannot be completely withdrawn because of the risk of graft rejection, a particular concern in lung, heart or liver transplant recipients. These immunosuppressive drugs may limit the expansion, persistence and efficacy of transferred EBV-CTLs. One of the most widely used immunosuppressive agents is FK506 whose effects are highly dependent on binding FKBP12 proteins, since T cells generated from FKBP12 knockout mice are completely resistant to the inhibitory effects of FK506. We have generated EBV-CTLs resistant to FK506 by knocking down FKBP12 using a small interfering RNA (siRNA) stably expressed from a retroviral vector. After extensively screening potential target sequences, we identified one, designed as siRNA4, that knocks down >90% of FKBP12 protein expression in T cell lines and also in EBV-CTLs, as assessed by Western blotting. We then generated two retroviral vector encoding for siRNA4/eGFP and irrelevant siRNA/eGFP, respectively. These vectors were used to transduce established EBV-CTL lines generated from 7 EBV-seropositive donors. Transduction efficiency was 46.3±22.5% and 55.4±27.5% for siRNA4 and irrelevant-siRNA, respectively. We measured the proliferation of transduced CTLs in the presence of FK506, in short term and long term cultures. Using a thymidine uptake assay, we found that the inhibiton of proliferation by increasing concentrations of FK506 was significantly diminished in siRNA4+ CTLs compared to control CTLs (41±4% inhibition for siRNA4+ CTLs vs 74± 2% for control CTLs). To evaluate the effects of knocking down FKBP12 in long-term cultures, control and siRNA4+ CTLs were stimulated weekly with the antigen (autologous EBV-LCL) with or without the addition of FK506 (5ng/ml) and low dose IL-2 (20U/mL). We found that the proportion of siRNA4+ CTLs increased over time not only as a percentage of GFP+ cells (from 46±22% to 89.4±5.3% after 5 stimulations) but also numerically (median fold expansion: 34.3, range 5–60). In contrast, control EBV-CTLs did not show any selection in culture, since the percentage of GFP+ cells remained unchanged (from 56±27% to 57±23.1%) and CTLs ceased to proliferate (median fold expansion: 2, range 0–5). Finally, we found that siRNA4+ CTLs retained their antigen specificity, having MHC-restricted cytotoxic activity against EBV-targets (66±22% vs 16±12% for autologous and allogenic LCL, respectively at an E:T ratio of 20:1 for siRNA4+ CTLs; 61±12% vs 15±12% for autologous and allogenic LCL, respectively, for control CTLs). Modified CTLs also maintained their production of IFNγ in response to specific EBV-peptides, as assessed by ELIspot assays. We are currently evaluating the in vivo expansion of genetically modified EBV-CTLs in the presence of FK506. In conclusion, we have developed a strategy that produces EBV-CTLs resistant to FK506. This strategy may be beneficial to improve EBV immune reconstitution in patients at high risk of developing post transplant lymphoma.

Download Full-text

Delayed Platelet Engraftment and Early Increased Creatinine after Stem Cell Transplant Predicts Sustained Remission in Pediatric Leukemia.

Blood ◽

10.1182/blood.v112.11.2159.2159 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2159-2159

Author(s):

Meera Sridhar ◽

Christopher C. Dvorak ◽

Rajni Agarwal ◽

Joshua D. Schiffman

Keyword(s):

Stem Cell ◽

Acute Leukemia ◽

Stem Cell Transplant ◽

Sustained Remission ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Platelet Recovery ◽

Allogeneic Hsct ◽

The Mean ◽

The Difference

Abstract Background: Acute leukemia is the most common pediatric malignancy, and high risk or relapsed disease accounts for the most frequent need for pediatric hematopoietic stem cell transplant (HSCT). The 5-year Event Free Survival for acute leukemia following HSCT approaches 55%, and we currently cannot predict which children will relapse following transplant. Prognostic determinants for allogeneic HSCT recipients are limited to risk status of underlying disease, type of transplant received (matched sibling donor vs. unrelated donor), and severity of graft vs. host disease (GVHD). Although some clinicians believe that an increase in RRT may actually reflect a better outcome, the prognostic significance of engraftment and regimen related toxicity (RRT) remains to be investigated. Patients receiving similar preparative regimens respond with varying degrees of toxicity which may reflect individual genetic variations and ultimately may determine their treatment outcome. Objective: To determine whether engraftment or RRT correlates with outcome (sustained remission vs. relapse) in pediatric HSCT patients with acute leukemia. Methods: A chart review was conducted on 96 consecutive pediatric allogeneic HSCT recipients with acute leukemia at Stanford University from 1996–2006 treated with TBI/ VP or TBI/CY. The previously validated Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was used to assess stomatotoxicity, hepatoxicity, and nephrotoxicity as indicators of RRT based on a 5-point Likert scale (0=no toxicity, 5=death). Toxicity scores were recorded within a 15 and 30 day period following HSCT to minimize toxicity attributed to GVHD. Time to hematological recovery also was assessed. An independent sample, two-tailed t-test was used to compare children in different outcome groups (relapse vs. sustained complete remission [CR]) for both combined total acute leukemia (TOTAL) and separate subtypes (ALL and AML). Finally, the percentage of patients with CR was calculated above and below the mean for any significant variables. Patients who died of treatment-related mortality (TRM) were removed from the analyses regardless of their remission status to avoid confounding. Results: Data were collected on 96 patients (ALL=53, AML=43). Twenty-one patients with TRM were removed, and the following number of HSCT patients analyzed: 75 TOTAL (CR=53, Relapse=22), 44 ALL (CR=29, Relapse=15), and 31 AML (CR=24, Relapse=7). CR patients took longer time to reach platelet recovery (P100) compared to relapsed pt’s for TOTAL (111 vs. 45 days, p=0.007), ALL (110 vs. 47 days, p=0.055), and AML (112 vs. 40 days, p=0.041). The TOTAL CR group also had higher creatinine-15 day scores (0.70 vs. 0.31, p=0.033) as did the AML CR group (0.83 vs. 0.28, p=0.05). This creatinine difference was no longer significant by Day-30. The percentage of CR patients above the mean P100 time to platelet recovery for each category was: TOTAL 89.5% (n=17/19, mean 97 days), ALL 82% (n=9/11, mean 92 days), and AML 100% (n=8/8, mean 104 days). The percentage of CR patients with creatinine-15 day scores above the mean was: TOTAL 79% (n=23/29, mean score 0.59) and AML 86% (n=12/14, mean score 0.7). The difference in denominators for each group is due to removal of patients without available data for specific variables or death due to TRM. Conclusion: This study represents one of the first attempts to methodically investigate whether engraftment and RTT are related to outcome in pediatric HSCT patients. Our retrospective analysis found delayed platelet engraftment (defined by platelet level of 100K/uL x 3 consecutive days) and higher creatinine-15 day values (less than 1.5 x normal) in leukemia patients who achieved sustained remission vs. those who ultimately relapsed. The difference in RRT scores between children who relapsed and those who did not may reflect differences in bone marrow and kidney exposure to previous chemotherapeutic agents; however, another explanation may be individual genetic variation in drug metabolism which leads to rapid drug clearance with lower RRT and subsequent relapse. Prospective studies are needed to validate our findings, in addition to high-throughput genomic screening to identify biological differences between children with different engraftment and RRT scores.

Download Full-text

Response to Adjuvanted Monovalent Influenza A (H1N1)v Vaccine In Allogeneic Hematopoietic Stem Cell Transplant Recipients

Blood ◽

10.1182/blood.v116.21.1269.1269 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1269-1269

Author(s):

Nathalie Dhedin ◽

Jacques-Olivier Bay ◽

Patricia Ribaud ◽

Mathieu Coudert ◽

Marie T Rubio ◽

...

Keyword(s):

Stem Cell ◽

Immunosuppressive Therapy ◽

Hematopoietic Stem Cell ◽

Influenza A ◽

Immunosuppressive Drugs ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Adjuvanted Vaccine ◽

Influenza A H1n1 ◽

Antibody Titers

Abstract Abstract 1269 Background: Influenza is a potentially serious infection after hematopoietic stem cell transplantation (HSCT). Prolonged immunosuppression leads to impaired immunity to infectious agents that contributes to the poor outcome after HSCT. Vaccination is the main prophylactic approach in individuals at an increased risk for severe influenza disease, but it is less effective in immunocompromised patients. Nevertheless, annual vaccination against influenza is recommended for HSCT recipients, starting at 6 months after transplant. In 2009, due to the emergence of a pandemic influenza A (H1N1)v virus, the development of safe and effective vaccines was a public health priority. Some oil-in-water-emulsion adjuvants were used in some 2009 influenza A (H1N1) vaccines to increase their immunogenicity. In France, the use of 2 doses of such vaccines was recommended for HSCT recipients. Methods: This study, conducted by the Société de Greffe de Moelle et de Thérapie Cellulaire, has evaluated the safety and the efficacy of an adjuvanted monovalent influenza A (H1N1)v vaccine in allogeneic HSCT recipients. Patients between the age of 18 and 65 years who were vaccinated from 3 months to 5 years post-transplant were included in the study. Patients in relapse of their hematological disease or receiving immunoglobulins were excluded. Patients were separated into two groups: patients with graft-versus-host-disease (GVHD) treated by immunosuppressive drugs (G1) and those without GVHD or immunosuppressive therapy (G2). Antibody responses were measured by means of a hemagglutination-inhibition assay on days 0, 21 and 42 after injection of the first dose of vaccine. Results: Seventy nine patients were included and 70 who received the 2 doses of adjuvanted vaccine (at day 0 and 21) were analyzed: 41 in G1, 29 in G2. Median patient age was 53 yr (range 21–65). Median interval between transplant and vaccination was11 months in G1 and 21months in G2. Fifty five % of patients received stem cells from peripheral blood and 44% received a myeloablative conditioning regimen. No severe post-vaccination side effect was observed, except in 2 patients who presented with an aggravation of their GVHD. No case of influenza A (H1N1)v infection was observed. At day 21 after the first dose, antibody titers, expressed as geometric means (GMT), were 20 and 69 in G1 and G2, respectively, whereas, they were 43 and 223, respectively, at day 42 after the second dose. By day 21, antibody titers of 1:40 or more were observed in 34% of patients in G1 and 73% in G2. By day 42, after the second dose of vaccine, antibody titers of 1:40 or more were observed in 47 % of patients in G1 and 86% in G2. The reverse cumulative distribution curves of antibody titers in serum at D0, D21 and D42 are shown in Figure 1. Conclusions: These data show that adjuvanted vaccine is safe in recipients of allogeneic HSCT. The humoral response was improved by the second dose of vaccine. The use of 2 doses of adjuvanted vaccine allows a seroprotection in almost all recipients without GVHD and immunosuppressive therapy and in half of the patients with GVHD and treated by immunosuppressive drugs. These data also suggest that addition of an adjuvant to improve the efficacy of a vaccine offers an advantage in recipients of HSCT. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Secondary hemophagocytic lymphohistiocytosis: a rare case report

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20191710 ◽

2019 ◽

Vol 7 (5) ◽

pp. 1963

Author(s):

Venkataraman Balamurugan ◽

Bharathi Vidhya Jayanthi

Keyword(s):

Cytotoxic T Cells ◽

Treatment Strategies ◽

Immunosuppressive Drugs ◽

Medical Emergency ◽

Cell Transplant ◽

Older Children ◽

Hematopoietic Stem ◽

Clinical Presentations ◽

Rare Case Report ◽

Life Threatening

Haemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic syndrome, characterised by hyperinflammation due to inherited or acquired defects in the immune function, leading to unchecked proliferation of histiocytes and lymphocytes resulting in multiorgan dysfunction. HLH can be primary (familial) occurring in young children caused by underlying genetic defects in natural killer cells/cytotoxic T cells or secondary HLH occurring in older children or adults following infections, rheumatological disorders or malignancies. HLH is a medical emergency, having varied clinical presentations and lacks a pathognomonic clinical or laboratory abnormality. Clinical presentations include unexplained fever, hepatomegaly, splenomegaly, skin rash, cytopenias, liver dysfunction, coagulation abnormality and neurological manifestations. It carries a poor prognosis. Early diagnosis based on HLH 2004 criteria and initiation of treatment is crucial in the management strategy, which is likely to improve the outcome of this life-threatening disease. The treatment strategies include immunosuppressive drugs, immunomodulatory therapy and autologous hematopoietic stem cell transplant in selected cases. Here with authors report a case of young adult, presenting with fever, thrombocytopenia, splenomegaly, and multi organ dysfunction, diagnosed as a case of secondary HLH based on the HLH 2004 guidelines.

Download Full-text

1188. Could Chlorehexidine (CHX) Bathing Decrease the Incidence of Carbapenem-Resistant Enterobacteria (CRE) Bacteremia in Previously Colonized CRE Hematopoietic Stem Cell Transplant Recipients (HSCT)?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1021 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S359-S359

Author(s):

Juan Diego Velez ◽

Fernando Rosso ◽

Jorge Cedano ◽

Barbara Lucia Mora ◽

Marly Orrego ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Protective Measure ◽

Cell Transplant ◽

Transplant Recipients ◽

Hematopoietic Stem ◽

Carbapenem Resistant ◽

The Difference ◽

Annual Proportion

Abstract Background CRE colonized patients that undergo HSCT have a higher incidence of CRE bacteremia, especially during the initial neutropenic period, with a high mortality rate. This situation is critical in countries highly endemic for CRE such as Colombia. It is necessary to find measures that decrease the occurrence of this infection, permitting a safer transplant. Daily CHX bathing could be effective reducing this risk. Methods Since March 2014 in our hospital in Cali, Colombia, all adult patients admitted to the HSCT unit were peri-rectal screened for CRE colonization, and then CHX daily bathing (CHX 4% soap or CHX 2% pads) was used regardless of the screening results. Prospectively all type of microorganism bacteremia were recorded from 2014 to 2017. We compare bacteremia, and CRE bacteremia rates between CRE colonized vs. non-colonized patients. We compared the annual proportion of CRE bacteremia in this two groups. Nonparametrical statistic χ2 for trend was used to compare the difference. Results We analyzed data collected from 155 patients from July 2014 to June 2017. There were 39.5% females, and the average age was 42 years, 60% were autologous, and 40% were allogeneic. The total of CRE colonized patients was 25/155 (16%), and the overall of bacteremia was 54/155 (34%). All type of microorganism bacteremia and CRE bacteremia were more frequent in CRE Colonized patients. (52% vs. 31% and 24% vs. 3,8%, RR: 6.24, 95% CI 2.06–18.8, P = 0.002). With the increase in compliance with CHX bathing, there was a decreasing trend in CRE bacteremia in the colonized patient, dropping from 50% during 2014, to 14% in 2017 (OR 0.167; P = 0.21). Conclusion Daily CHX bathing in the CRE colonized patient reduce the incidence of CRE bacteremia in HSCT patients. We propose this intervention as a significant protective measure in CRE colonized hospitalized patients. Disclosures All authors: No reported disclosures.

Download Full-text

High-Dose Cyclophosphamide In Combination With G-CSF Versus G-CSF Alone For Mobilization Of Hematopoietic Stem Cells After Induction Therapy Including Velcade, Cyclophosphamide and Dexacort

Blood ◽

10.1182/blood.v122.21.5369.5369 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5369-5369

Author(s):

Noam Benyamini ◽

Irit Avivi ◽

Eldad J Dann ◽

Tsila Zuckerman ◽

Lavi Noa ◽

...

Keyword(s):

Stem Cell ◽

Induction Therapy ◽

Conflicts Of Interest ◽

Young Patients ◽

High Dose ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Cd34 Cells ◽

Significant Difference ◽

The Difference

Abstract Introduction Even in the era of novel agents, high-dose chemotherapy followed by autologous stem cell transplant (ASCT) is considered to be an essential part of treatment for young patients with multiple myeloma (MM), providing durable responses. Currently, VCD (velcade, cyclophosphamide and dexacort) is one of the most commonly employed induction regimens. High-dose cyclophosphamide (HDC), often used in stem cell (SC) mobilization in conjunction with G-CSF, is associated with adverse events and only modest efficacy against myeloma. An alternative mobilization regimen, using G-SCF alone, has been recently suggested to provide adequate SC collection with less toxicity. Nevertheless, the efficacy and safety of using G-SCF alone after VCD induction have not been fully explored. The current study compares the safety and efficacy of mobilization using HDC-G-CSF versus G-CSF alone in MM patients treated with VCD as induction therapy. Methods The study was approved by the Institutional Review Board of the Rambam Medical Center (Approval # 0110-13 RMB). Data on all consecutive newly diagnosed transplant-eligible MM patients, treated with VCD between 2009 and 2012, were retrospectively reviewed. Eligibility criteria were: VCD induction followed by SC mobilization, either with G-CSF or HDC-G-CSF, with subsequent high-dose melphalan (200 mg/m2) and ASCT. The mobilization protocol was chosen at the discretion of the treating physician. Evaluated data included patient characteristics, SC collection and engraftment related parameters. For statistical analysis, Mann-Whitney non-parametric test for 2 independent groups was used. Results 79 patients were included: 50 mobilized with HDC-G-CSF, and 29 with G-CSF alone. There were no statistically significant differences in terms of patient demographic and MM-related characteristics (MM type, ISS, number of VCD cycles, and disease status at the end of induction) between the 2 cohorts. The first day of SC collection yielded a median of 14.6x106 (range 1.9 -10.1) vs 5.3x106 CD34 cells/Kg (range 0.6-37.7) in the HDC-G-CSF vs the G-CSF groups (p=<0.001). A significantly higher total CD34 collection was obtained in the HDC-G-CSF treated patients (15.9 x 106 vs 8.1x106 CD34 cells/Kg, respectively, P<0.001). Additionally, a bivariate analysis showed that male gender and platelet count (>150,000/mL) prior to mobilization had a significant impact on the outcome of SC collection. The percentage of patients needing more than one day of leukopheresis following HDC-G-CSF and G-CSF was 42% and 83%, respectively. During treatment and mobilization, 20% of patients in the HDC-G-CSF cohort were hospitalized due to neutropenic fever, while none of the patients from the G-CSF group required hospitalization (P<0.011). In all patients apart from one (G-CSF group), at least the minimum of CD34 cells/Kg required to perform a transplant (2x106 CD34 cells/Kg) was collected. Moreover, most patients succeeded in collecting >5x106 CD34 cells/Kg (96% and 93.1% in HDC-G-CSF and G-CSF groups, respectively). Notably, the difference between the groups achieved statistical significance only in collection of >8x106 CD34 cells/Kg (88% and 55.2% of patients treated with HDC-G-CSF and G-CSF, respectively). The median amount of cells administered at transplantation was 7.9x106 and 4.9x106 for patients mobilized with HDC-G-CSF vs G-CSF, respectively, reflecting the difference in the total amount of collected cells. Despite the variation in the amount of transplanted cells, no significant difference in parameters of the transplant outcome was revealed between the 2 cohorts: time to neutrophil engraftment (>500 cells/µl) at a median of 12 days in both groups and platelets engraftment (>25,000 cells/µl) at a median of 14.5 vs 13 days in the HDC-G-CSF and G-CSF groups, respectively. The length of hospitalization, approaching 17 days, did not differ between the 2 groups. Conclusions Mobilization using HDC-G-CSF results in a higher total amount of collected CD34 cells and requires less days of leukophersis. Nevertheless, G-CSF alone provides a sufficient number of SC for transplantation in almost all patients, and this approach is much safer than treatment with HDC-G-CSF. Since engraftment results are identical with the 2 mobilization methods, the use of G-CSF alone could be considered as a preferable cell mobilization protocol in patients previously exposed to VCD induction. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Humoral Response to BNT162b2 mRNA Covid19 Vaccine in Peritoneal and Hemodialysis Patients: a Comparative Study

10.1101/2021.06.14.21258113 ◽

2021 ◽

Author(s):

Rui A Duarte ◽

Marisa Roldão ◽

Cátia Figueiredo ◽

Ivan Luz ◽

Francisco Ferrer ◽

...

Keyword(s):

Demographic Data ◽

Humoral Response ◽

Healthy Population ◽

Dialysis Patients ◽

Absolute Value ◽

Final Study ◽

Dialysis Vintage ◽

Comorbidity Burden ◽

Antibody Titers ◽

Comorbidity Index

Introduction Generalized immunization against COVID19 has become the cornerstone in prevention of associated severe acute respiratory syndrome. Maintenance dialysis patients (MDP) are at higher risk of both exposure and mortality from the disease. Efficacy and security of BNT162b2 vaccine is well documented for the general population, but not in MDP, particularly in peritoneal dialysis (PD) patients. This study aims to compare humoral response between HD and PD patients. Materials and Methods Observational prospective study including MDP on HD or PD program from a Portuguese middle-sized Nephrology Center, who received BNT162b2. Specific anti-Spike IgG was measured as arbitrary units per milliliter (AU/mL) on two separate occasions: 3 weeks after the first dose and 3 weeks after the second. The two modality groups were compared both for absolute value and number of non-responders (NR) after both inoculations. Demographic data was also obtained and compared. Results Of 73 patients enrolled, 67 were eligible for the final study: 42 HD and 25 PD patients. PD group developed significantly higher antibody titers both after first (Med 5.44 vs 0.99; p<0.01) and second dose (Med 170.43 vs 65.81; p<0.01). HD status was associated with non-responding after the first dose (Phi=0.383; p<0.01), but not after the second one (p=0.08). Age, Charlson Comorbidity Index and dialysis vintage were lower in the PD group (p<0.01; p=0.02; p<0.01, respectively). Conclusion This study demonstrated a better humoral response to immunization with BNT162b2 in PD patients, when comparing to HD patients, after both inoculations. Both groups showed substantial humoral response after just one dose of the vaccine. Older age and higher comorbidity burden may explain the relative immunogenicity deficit, probably in a superior degree comparing with age matched healthy population.

Download Full-text