Enterovirus-associated deafness and myositis in an immunocompromised patient with in vivo and in vitro efficacy of intravenous immunoglobulins and remdesivir: Case report.

Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology

We have read with great interest the report by Evens et al (2008) on the result of a phase II study of intensive chemotherapy followed by consolidative autologous stem cell transplant (SCT) for newly diagnosed mantle cell lymphoma (MCL) patients. In this study, an intensive induction chemotherapeutic regimen consisted of alternating cycles of cyclophosphamide, teniposide, doxorubicin and prednisone with vincristine, high dose methotrexate and cytarabine was used. Thirteen patients ≤65 years then proceeded to consolidative high dose busulfan/cyclophosphamide followed by autologous SCT. With this approach, the 5-year event-free survival (EFS) and overall survival (OS) was 54% and 75%, respectively. These results are encouraging, especially taking into account the long follow-up of the study. Further analysis of the whole group of 25 patients treated with this induction regimen showed that the one single factor predicting for improved survival was consolidative autologous SCT. High dose chemotherapy followed by autologous SCT has been investigated previously, but the results have been conflicting (Andersen et al, 1997;Khouri et al, 2003; Dreger et al, 2000). Furthermore, except for the report by Evens et al (2008), the median follow-up of these patients have generally been short. The conflicting results are probably related to the use of different chemotherapeutic agents as conditioning regimens for the transplant and also to different post-transplant therapy. We have chosen to induce newly diagnosed advanced stage MCL with R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone, rituximab), followed by a consolidative autologous SCT after single agent high dose melphalan. This regimen has not been previously tested in MCL. Furthermore, we reasoned that, as most patients relapse within the first two years after transplant, maintenance rituximab therapy might also be useful during the first two years after autologous SCT. Because the tumor load following autologous SCT is low, the patients may only need intermittent low dose rituximab over a 2 year-period. Following consent, eight consecutive patients with newly diagnosed advanced Stage III or IV MCL were treated. The clinical characteristics of these patients are shown in Table I. There were five males and three females, with a median age of 61 years (range 47–72 years). One patient had Stage III and the other seven had Stage IV disease. All eight patients received remission + 2 cycles of R-CHOP as induction chemotherapy. Autologous stem cells were harvested upon recovery from the last cycle of R-CHOP and autologous SCT carried out within 6 weeks from the last cycle of R-CHOP. High dose intravenous melphalan (200 mg/m2) was administered, followed 24 h later by the infusion of a minimum of 2 × 106/kg of CD34+ autologous stem cells. Rituximab maintenance therapy was initiated at a dose of 375 mg/m2, given as a single infusion once every three months starting Day +100. This approach was well tolerated. Despite the higher median age of the patients, treatment-related mortality was 0%. Complete remission (CR), documented clinically and by a positron emission tomography scan, was achieved in all eight patients before autologous SCT. Median time to engraftment following autologous SCT was 13 d (range 9–30 d). Not surprisingly, due to the older age of the group, two patients died from non-lymphoma causes, without evidence of lymphoma. One patient died due to metastatic breast cancer at 34 months and another one to myocardial infarction at 40 months. Lymphoma relapse occurred in only one patient, 28 months from diagnosis and during the rituximab maintenance period. This patient is still alive and is being re-induced with velcade/dexamethasone. As of February 2008, with a median follow-up of 54 months (range 28–76 months), the EFS and OS for the group was 57% and 67%, respectively (Fig 1). Adverse effects were as expected from the high dose melphalan, except that delayed immunoglobulin reconstitution, as reported previously (Lim et al, 2005), was observed in all eight patients. The delayed immunoglobulin reconstitution persisted beyond the rituximab maintenance period (Lim et al, 2008). Four of these hypogammaglobulinemic patients had recurrent infections (three with recurrent respiratory tract infection and one with a chronic diarrhoea that was Vancomycin sensitive) and three required monthly intravenous immunoglobulin replacement. Kaplan–Meier estimate of event-free survival (EFS) and overall survival (OS) of patients. The results presented here are, therefore, extremely encouraging for a group of patients who normally have a very poor clinical outcome, and support the notion, as suggested by Evens et al (2008), of an early consolidative autologous SCT for these patients. This approach is well tolerated and could be applied to even older patients.

Background Chronic wound infection has become a major healthcare burden globally. The colonized microbiome features and correlation between bacteria and fungi have not been listed. Methods In this study, we enrolled 38 acute wound infection and 28 chronic wound infection patients. The wound swabs sampling at admission were tested by metagenomic next-generation sequencing. Microbial community characteristics in wound infection patients and bacteria-fungi correlations in chronic wound infection patients were analyse after filtering background organisms.Figure 1.Flow chart Results We found that wound microbiome in chronic wound infection patients had higher abundance of Pseudomonas aeruginosa than that in acute wound patients. Meanwhile, microbes with high relative abundant in chronic infection wounds were less significantly association with plasma inflammation factors compared with those in acute infection wounds. Finally, we investigated the association between fungi and bacteria in chronic infection patients and found that relative abundance of Pseudomonas aeruginosa was negatively associated with that of Candida albicans.Figure 2.Comparison of bacteria species relative abundance between groups.Barplot of average relative frequencies of genera. Only genera>1% of relative abundance in wound were represented. C= chronic infection wound group, NC= acute infection wound groupFigure 3.Analysis of Linear Discriminant Analysis (LDA) Effect Size in groups.The bar graph showed pathogens with LDA score log10 >5 in two groups. C= chronic infection wound group, NC= acute infection wound group.Figure 4.Fungi-bacteria network in patients with chronic infection wound.Green dots: bacteria; Blue dots: fungi; red edge: positive correlation; green edge: negative correlation. Relative abundance of Pseudomonas aeruginosa was negatively associated with that of Candida albicans highlighted with red box. Conclusion Our metagenomic sequencing results of wound supported that Pseudomonas aeruginosa may be the biomarker of chronic wound infection and have interaction with candida albicans. Disclosures All Authors: No reported disclosures

Single Vs. Tandem Autologous Stem Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Real-World Multi-Center Study from the German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST)

In the article "Sporadic late-onset nemaline myopathy: Clinical spectrum, survival, and treatment outcomes," Drs. Naddaf et al. reported that the overall survival among 28 patients with sporadic late-onset nemaline myopathy (SLONM)—identified by retrospective chart review—did not seem to be affected by the presence of a monoclonal protein (MP). They concluded that initial treatment with intravenous immunoglobulin (IVIg) was reasonable in all patients, followed by autologous stem cell transplant (ASCT) or chemotherapy as second-line therapy in patients with an associated MP. In response, Drs. Chahin and Karam suggest clarifying the degree of weakness and disability of those patients who received IVIg vs those who received ASCT because this could result in selection bias. They report that in their experience, patients with SLONM and MP with a severe phenotype who were treated with IVIg initially appeared stable over 6 months but then rapidly deteriorated—becoming too weak for ASCT—and died. They also cite a previous study that showed worse survival in patients with MP and posit that the absence of such a difference in this study may relate to the recent approach of aggressive treatment of such patients. In the absence of a study comparing IVIg and ASCT in such patients, they conclude that some patients with aggressive SLONM may be best treated with ASCT directly. Responding to these comments, Drs. Naddaf et al. reported no difference in the Neuropathy Impairment Score-Weakness at presentation between patients who received IVIg vs ASCT. They acknowledge the inherent limitations of referral bias and retrospective design but note that severely affected patients were still among those referred to their institution who showed good response to IVIg, with none rendered ineligible for ASCT by previous treatment failure. They counter that given the risks of morbidity, mortality, and other post-ASCT side effects, IVIg should still be the first-line treatment in the absence of evidence of superiority of ASCT, with ASCT considered for patients not responding after 2–3 months. This exchange demonstrates the clinical equipoise regarding the choice of IVIg vs ASCT as first-line therapy for patients with SLONM, particularly in the presence of MP. In the article "Sporadic late-onset nemaline myopathy: Clinical spectrum, survival, and treatment outcomes," Drs. Naddaf et al. reported that the overall survival among 28 patients with sporadic late-onset nemaline myopathy (SLONM)—identified by retrospective chart review—did not seem to be affected by the presence of a monoclonal protein (MP). They concluded that initial treatment with intravenous immunoglobulin (IVIg) was reasonable in all patients, followed by autologous stem cell transplant (ASCT) or chemotherapy as second-line therapy in patients with an associated MP. In response, Drs. Chahin and Karam suggest clarifying the degree of weakness and disability of those patients who received IVIg vs those who received ASCT because this could result in selection bias. They report that in their experience, patients with SLONM and MP with a severe phenotype who were treated with IVIg initially appeared stable over 6 months but then rapidly deteriorated—becoming too weak for ASCT—and died. They also cite a previous study that showed worse survival in patients with MP and posit that the absence of such a difference in this study may relate to the recent approach of aggressive treatment of such patients. In the absence of a study comparing IVIg and ASCT in such patients, they conclude that some patients with aggressive SLONM may be best treated with ASCT directly. Responding to these comments, Drs. Naddaf et al. reported no difference in the Neuropathy Impairment Score-Weakness at presentation between patients who received IVIg vs ASCT. They acknowledge the inherent limitations of referral bias and retrospective design but note that severely affected patients were still among those referred to their institution who showed good response to IVIg, with none rendered ineligible for ASCT by previous treatment failure. They counter that given the risks of morbidity, mortality, and other post-ASCT side effects, IVIg should still be the first-line treatment in the absence of evidence of superiority of ASCT, with ASCT considered for patients not responding after 2–3 months. This exchange demonstrates the clinical equipoise regarding the choice of IVIg vs ASCT as first-line therapy for patients with SLONM, particularly in the presence of MP.

Passive immunization against COVID-19 by anti-SARS-CoV-2 spike IgG in commercially available immunoglobulin preparations in severe antibody deficiency

Long-Term Clinical and Molecular Remissions in Patients with Mantle Cell Lymphoma (MCL) Following High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT)

Rituximab Maintenance Therapy after Autologous Stem Cell Transplantation Improves Survival of Patients with Mantle Cell Lymphoma

Primary immunodeficiencies (PIDs) are genetically determined diseases with irreversible disorders in the immune system. A significant part of PIDs are immunodeficiencies with disordered or completely absent synthesis of specific antibodies (agammaglobulinemia, common variable immunodeficiency, etc.). The main pathogenetic treatment for these patients consists of regular monthly intravenous immunoglobulin (IVIG) infusions. The immunoglobulin is not a synthetic product - it is manufactured from pooled donor plasma and is in need of high purification and virus inactivation: these procedures determine high cost of the final product. Because of high cost of IVIG preparations, the patients sometimes cannot have them free (within the framework of obligatory medical insurance or other insurance variants). We analyzed the costs of therapy and follow-up of 20 patients with PIDs (7 patients with common variable immunodeficiency and 13 patients with agammaglobulinemia), aged 20 months to 16 years, for 2 years without IVIG and for the same period with IVIG therapy. Regular replacement therapy with IVIG (Octagam 5%, immunoglobulin human normal, solution for intravenous administration, “Octapharma Pharmazeutika Produktions, ges m.b.H.”, Austria) in patients with primary antibody deficiency syndromes led to reduction in the number of infectious episodes, need in hospitalization and outpatient care, and expenditures for sick leave payments. Analysis of the costs of therapy before the beginning of pathogenetic therapy and during replacement IVIG therapy showed that the costs of symptomatic therapy and other PIDs' complications were lower (340 905 ± 191 600 rubles per patient) in the group of patients with early diagnosis and few infectious episodes in comparison with the pathogenetic therapy with the use of IVIG (995 890 ± 462 600 rubles per patient: p < 0.001). Pathogenetic IVIG therapy in patients with late diagnosis and chronic infections led to a significant reduction of the treatment costs (1.191 020 ± 494 700 rubles per patient before IVIG and 782 214 ± 47 790 during IVIG therapy: p = 0.05). These results indicate economic efficacy of adequate pathogenetic therapy of PIDs with the use of IVIG preparations.

The aim of this prospective, single-arm study was to test the efficacy and tolerability of autologous stem cell transplantation (auto-SCT) combined with in vivo rituximab purging and post-transplant rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (DLBCL). This study included 12 DLBCL patients aged 18-65 years with an International Prognostic Index ≥2. The patients received 4-6 cycles of induction therapy consisting of rituximab plus cyclophosphamide, adriamycin, vincristine and prednisone followed by salvage therapy prior to stem cell mobilization. This regimen was followed by rituximab maintenance therapy (375 mg/m(2) every three months for two years). Prior to auto-SCT, six patients (50%) achieved complete remission (CR) and six (50%) achieved unconfirmed complete remission (CRu). Three months after transplantation, 11 patients (91.7%) achieved CR and one achieved CRu. After two cycles of rituximab maintenance therapy, all 12 patients achieved CR. Long-term CR was achieved by 10 patients, while two experienced relapse at 14 and 20 months after the end of rituximab maintenance therapy. The median follow-up period was 44 months (range 35-61). Disease-free survival was noted in 10 patients, while two experienced relapse. The three-year overall survival (OS) and progression-free survival (PFS) were 100 and 83%, respectively. Prolonged hypogammaglobulinemia occurred in two patients, although no increase in major infections was observed. Hepatitis B surface antigen was continuously negative in all 12 patients. Our results demonstrated that auto-SCT combined with in vivo rituximab purging and post-transplant rituximab maintenance is safe and effective, and may extend OS and PFS in younger high-risk DLBCL patients.

Multiple myeloma (MM) is a malignant hematological disease originating from plasma cells that remains incurable. Autologous stem cell transplantation (ASCT) is an important treatment method for MM. With the development of new drugs, the treatment of MM patients who meet the ASCT criteria has significantly improved, and the median survival time has increased by 8-10 years. The current treatment for MM patients who meet the ASCT criteria consists mainly of the following stages: induction therapy, stem cell collection, stem cell transplantation, and consolidation and maintenance therapy. Even today, long-term disease control remains the goal of MM treatment in clinical practice. In the era of new drugs, early ASCT still results in longer progression-free survival (PFS) and is currently the standard treatment method for young newly diagnosed multiple myeloma (NDMM) patients. Moreover, tandem transplantation can be considered for MM patients with high-risk cytogenetics. This review discusses mainly the role of ASCT in MM, the conditions for patient transplantation, the induction chemotherapy regimen before transplantation, the conditioning regimen, the timing of transplantation, and the effectiveness of tandem transplantation, including maintenance and salvage ASCT after transplantation.

ALL-051: Outcomes of Treatment of Acute Philadelphia-Positive Acute Lymphoblastic Leukemia with Autologous Transplant of Hematopoietic Stem Cells at San Juan De Dios Hospital from 2014 to 2019

Despite advancements in the treatment of diffuse large B-cell lymphoma, including CAR T-cell therapy, TP53 mutations remain a significant negative prognostic factor in patients with relapsed/refractory diffuse large B-cell lymphoma. The combination of autologous stem cell transplantation and CAR T-cell therapy may enhance long-term prognosis and reduce adverse effects, including severe cytokine release syndrome. This case report presents a 41-year-old man with relapsed/refractory diffuse large B-cell lymphoma harboring TP53 mutations who underwent autologous stem cell transplantation combined with CD19 CAR T-cell therapy. Two years posttreatment, the patient remains in sustained complete remission, highlighting the potential efficacy of this combination approach for relapsed/refractory diffuse large B-cell lymphoma with TP53 mutation.

Treatment of B-cell non-Hodgkin's lymphomas (NHL) with either Rituximab alone or in combination with cytotoxic chemotherapy has been effective without major side effects. Thus, Rituximab maintenance therapy after autologous peripheral blood stem cell transplantation (PBSCT) might represent an improvement in NHL therapy. We therefore retrospectively analyzed the efficacy and side effects of monthly long-term Rituximab maintenance therapy after PBSCT in 27 patients with NHL. In median 10 infusions of Rituximab were given after PBSCT in time intervals of 1 month. Molecular monitoring of t(14;18) was performed using nested as well as quantitative real time polymerase chain reaction (RT-PCR) based on the LightCycler technology. Side effects according to common toxicity criteria (CTC) > II did mainly affect the hematopoietic system. In total, 10 patients (37%) suffered form grade III-IV hematotoxicity. Except for two patients with cutaneous Varicella-Zoster infection no serious infectious complications (CTC grade III/IV) occurred. No patient died because of treatment-related causes. This adverse event data compared favorably to the published data. Three patients had t(14;18) nested RT-PCR positive results before Rituximab therapy and converted to negativity after Rituximab therapy. We conclude that a prolonged Rituximab maintenance therapy after PBSCT with monthly administration is reliable and safe.

Rituximab Maintenance Therapy After Autologous Stem Cell Transplantation Prolongs Progression Free Survival In Patients With Mantle Cell Lymphoma