The impact of community-acquired respiratory viral infections (CARVIs) in the transplant population has been highlighted by the recent coronavirus disease 2019 (COVID-19) pandemic. Patients undergoing haematopoietic stem cell transplantation (HCT) following acute COVID-19 experienced significant morbidity and mortality. Few guidelines and reports suggest that HCT is deferred during persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity during and after infection, and is feasible only in fully recovered patients [1, 2]. However, those with high-risk haematological malignancies often progress and succumb to their disease without timely HCT. These two opposing pressures must therefore be reconciled, yet data are sparse on the optimal timing and safety of HCT that needs be performed during or immediately following acute COVID-19 infection.
In this study at Singapore General Hospital, the largest tertiary transplant centre in Singapore, the outcome of patients who underwent HCT following COVID-19 in the preceding 120 days or with active COVID-19 infection during transplant was analysed. A retrospective analysis of transplant-related outcomes in consecutive patients admitted for planned HCT between September 2021 and April 2022 was conducted. COVID-19 was detected by SARS-CoV-2 RNA by polymerase chain reaction (PCR) on nasopharyngeal swab. Patients diagnosed with COVID-19 within 120 days prior to stem cell infusion were included in the study.
We identified 10 allogeneic and 1 autologous HCT patients. Median interval between diagnosis of COVID-19 to HCT infusion was 53 days (range 1–118). Median duration of COVID-19 infection (defined by time to negative PCR) was 20 days. Six patients tested negative by PCR and 2 were prolonged low-level viral shedders, prior to HCT. Two patients were diagnosed with COVID-19 while receiving conditioning chemotherapy prior to HCT infusion, at days −1 and −3, respectively.
All allogeneic HCT patients were fully vaccinated with two doses of mRNA vaccines (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) prior to infection. Median receptor binding domain IgG serology titre (Abbott assay) in vaccinated patients was 1301 AU/mL at the time of COVID-19 diagnosis. COVID-19 disease severity by National Institutes of Health (NIH) guidelines [3] was mild in nine patients, moderate in one patient and critical in one patient. Eight patients received antivirals with or without concurrent monoclonal antibodies (mab; sotrovimab, n = 4; casirivimab–imdevimab, n = 1).
Patient characteristics and outcomes are summarised in Table 1, and transplant-related details are provided in Supporting Information Table 1. Two patients died of non-relapse pulmonary complications on days +43 and +50 post-HCT. There were no instances of grade III–IV acute graft versus host disease and no evidence of SARS-CoV-2 reinfection or late complications, or increase in vira
Dear Editor,
We would like to share ideas on the publication “Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients [1].” Researchers compared patients based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology in order to examine the outcomes of hematologic malignancy (HM) patients with SARS-CoV-2 infection from January 2022 to March 2023 in this retrospective single-center analysis. Of the 112 patients in the research, 39% had a negative serology for SARS-CoV-2. Comparing seronegative individuals to seropositive patients, the findings showed that the former were older, had a higher likelihood of a lymphoid neoplasm, had anti-CD20 medication, and had a more severe illness. Additionally, a Kaplan–Meier study revealed that patients who tested negative for COVID-19 were more likely to experience respiratory failure, require mechanical ventilation, and die from the virus.
This study's retrospective approach, which can create biases and restrictions in data collection and analysis, is one of its drawbacks. Furthermore, the research was carried out at a single facility, which can restrict how broadly the results can be applied to other demographics. Additionally, it is possible that the sample size of 112 patients was insufficient to make firm conclusions, particularly when comparing the outcomes of HM patients who were seronegative and those who were seropositive. Furthermore, the study did not look into any confounding factors that might have affected the patients' results.
Conducting a bigger multicenter prospective study to validate the results of this study and improve the generalizability of the results could be one of the next directions for this area of research. Furthermore, analyzing the effects of various treatment modalities on outcomes in SARS-CoV-2-infected HM patients may offer insightful information for clinical practice. Furthermore, investigating the immune response and its impact on illness outcomes and progression in seronegative HM patients may aid in deciphering the underlying processes of COVID-19 in this particular cohort. Last but not least, examining the long-term consequences of COVID-19 for HM patients, such as the likelihood of relapse and late sequelae, may yield crucial data for patient management and post-treatment care.
Ideas, writing, analyzing, and approval (50%): Hinpetch Daungsupawong. Ideas, supervision, and approval (50%): Viroj Wiwanitkit.
The authors declare no conflicts of interest.
The authors received no specific funding for this work.
The authors have confirmed that ethical approval statement is not needed for this submission.
The authors have confirmed that patient consent statement is not needed for this submission.
The authors h
Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS-IB-1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, p = 0.045; HR = 3.64, 95%CI 1.40-9.44, p = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.
Teclistamab is a B-cell maturation antigen (BCMA)-directed bispecific T-cell engager approved for relapsed-refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) are well-documented treatment -related adverse events of teclistamab. The prescribing information recommends step-up dosing on days 1, 4, and 7 with 48–72 h of inpatient observation after each dose to monitor for CRS. This leads to a more than weeklong hospital stay, adding to the cost of therapy, resource utilization, and patient inconvenience. Here, we present a single center retrospective analysis addressing the safety and utility of a condensed step-up dosing schedule for teclistamab. All patients who were treated with teclistamab from November 2022 to August 2023 at the Medical University of South Carolina were included in the analysis. Patients received subcutaneous (SC) teclistamab with step-up doses (0.06 and 0.3 mg/kg) separated by either 2 or 3 (48–72 h) before the administration of the first full (1.5 mg/kg) dose (days 1, 3, and 5 ‘condensed’ schedule or days 1, 4, and 7 ‘standard’ schedule, respectively). All patients were hospitalized for the two step-up doses and first full dose of teclistamab and received pre-medications prior to each dose. Patients could be discharged after a minimum of 24 h following the full dose, if they did not have any CRS or ICANS. Relevant data regarding incidence, severity, and onset of CRS was collected. Statistical analysis was completed to assess the probability of fever with the first full dose of teclistamab based on incidence of fever with previous doses. A total of 25 patients were included in the analysis. Twenty-eight percent (7/25) of patients underwent the standard step up while the remaining 72% (18/25) underwent a condensed step up of teclistamab. More than half (53%, 13/25) of the patients experienced CRS during step up dosing. Grades 1 and 2 CRS occurred in 48% (12/25) and 4% (1/25) patients, respectively. Of the 13 patients that experienced CRS, 30% (4/13) fevered with the first dose, 84% (11/13) fevered with the second dose, and one patient developed fever after the third dose. The negative predictive value of being ‘fever free’ after doses 1 and 2 and remaining ‘fever free’ throughout hospitalization was 0.92. The median length of hospital stay among the 1, 3, and 5 step up group was 6 days (6–25) and 70% (14/20) of patients were discharged from the hospital within 7 days of treatment initiation. This report demonstrates the utility of a condensed step-up schedule for teclistamab initiation. The schedule was found to be safe and reduced hospital length of stay. These results should prompt consideration of shorter hospital stays for patients who do not experience CRS and raise the possibility of outpatient administration with close observation.
Talquetamab is an approved therapy for relapsed multiple myeloma. This study examined dysgeusia and weight loss occurrences, alongside investigating symptom reversibility post-treatment cessation. Dysgeusia was prevalent, persisting in 15% of patients. On average, patients lost 6% of their weight during treatment, with weight loss persisting in about half of the patients post-discontinuation. Weight loss and dysgeusia are important adverse events to consider while on talquetamab treatment. Extending dose intervals can potentially prevent such adverse events and should be studied in future prospective clinical trials.
A 29-year-old Caucasian man was treated for acute myeloid leukemia. He underwent allogeneic stem cell transplantation from an unrelated donor. Six months after the transplant, he relapsed, and salvage chemotherapy was administered, including azacitidine and venetoclax. Vitamin C was added to enhance the azacitidine effect. Rasburicase and allopurinol were given to prevent tumor lysis syndrome. The following day, the patient developed a fever, and an influenza infection was diagnosed and treated with oseltamivir.
On the third day of azacitidine treatment, his blood test showed a hemoglobin level of 6.8 g/dL (range: 13.3–17.6), mean corpuscular volume of 110.6 fL (range: 80.1–99.8), indirect hyperbilirubinemia (indirect bilirubin at 6.35 mg/dL), an undetectable haptoglobin, and a high level of lactate dehydrogenase (1464 IU/L, range: 120–246). These features were suggestive of a hemolytic crisis. A blood smear was performed, showing no schizocytes but revealing hemighost red blood cells (Figure 1), suggesting a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Other causes of hemolysis were excluded, including deficiencies and thrombotic microangiopathy.
The patient had no personal or family history of a hemolytic crisis. The G6PD activity was low, but the patient had received red blood cell transfusions. The graft donor came from the Middle East. After a few days, the G6PD deficiency was confirmed by the donor medical team, but this information was not transmitted before the allogeneic stem cell transplantation.
G6PD deficiency, also known as favism, is an X-linked hereditary disease commonly found in African, Asian, Mediterranean, and Middle Eastern regions. It is the most common human enzyme defect, affecting more than 500 million people worldwide. Hemolysis mainly occurs after infection or exposure to oxidant drugs. Rasburicase is known to be a strong trigger of hemolysis in G6PD-deficient patients.
To our knowledge, this represents the first documented instance of a hemolytic crisis arising from acquired G6PD deficiency subsequent to an allogeneic stem cell transplantation. G6PD deficiency may be transmitted either from a symptomatic donor, regardless of gender, or from an asymptomatic heterozygous female donor following lyonization. The case report highlights the difficulty of establishing a diagnosis of a congenital disease, especially in a low-prevalence country. It underscores the importance of a correct donor evaluation and the necessity of good communication between the patient/donor transplant teams.
Dr. Vô Quentin: data collection, writing, and editing of the manuscript. Dr. Beshir Alaa: data collection. Dr. Collinge Elodie: critical feedback and manuscript revision. Dr. Khourssaji Mehdi: biological analysis and clinical photography. All authors read and approved the final manuscript.
The authors declare no conflict of interest.
The authors received no specific funding for this work.
<Acquired von Willebrand syndrome (AVWS) is a bleeding disorder in which an underlying condition induces a quantitative or qualitative deficiency in the von Willebrand factor. This case demonstrates the rare diagnosis of AVWS due to an Immunoglobulin G monoclonal gammopathy in an elderly woman who presented with significant gastrointestinal bleeding. Originally thought to be type 1 von Willebrand disease, this case provides a cautious example to clinicians that without a detailed history or an understanding of the associated laboratory work-up, AVWS may be missed with potentially fatal consequences. Fortunately, AVWS was recognized and treated with intravenous immunoglobulin with a resolution of bleeding.
An 82-year-old man was referred for a 13 kg weight loss and an erythroderma evolving for 2 months. Clinical examination revealed an asteatotic eczema (AE) predominant on the trunk (Figure 1A) associated with palmoplantar keratoderma and supracentimetric cervical polyadenopathy. Biologically, the patient presented with 11 g/dL nonregenerative normocytic anemia, neutrophilic polynucleosis of 12.4 G/L, lymphopenia of 0.4 G/L, and hypoalbuminemia of 21 g/L. Imaging (computed tomography [CT] scan and positron emission tomography (PET)-CT) confirmed supradiaphragmatic hypermetabolic polyadenopathy. Skin biopsy showed ichthyosiform dermatosis suggestive of a paraneoplastic process (Figure 1C). Node biopsy confirmed the diagnosis of classic Hodgkin lymphoma (Figure 1D). The patient was treated with brentuximab vedotin alone for the first two perfusions which permitted AE clinical complete remission (CR) (no PET-CT reevaluation was available) and then combined with pembrolizumab for treatment intensification which was effective on both the lymphoma and the dermatosis, and which permitted a CR after four cycles. Treatment was stopped after four doses of brentuximab vedotin and two doses of pembrolizumab because of CR and immunomediated toxicities (nephropathy and pancreatitis). He is still in CR after 10 months of follow-up.
A 78-year-old man was hospitalized for a diffuse AE associated with palmoplantar keratoderma (Figure 1B). A single firm and painless right inguinal adenopathy measuring 3 cm was found at clinical examination. The CT scan showed primitive and external right iliac adenopathies. Node biopsy was consistent with Epstein-Barr virus-negative classic Hodgkin lymphoma. The patient died suddenly of unknown cause before beginning the treatment.
AE, first described in 1907 by Bocq, is a particular form of xerosis affecting older patients, which results from a depletion of the secretion of the sebaceous and sweat glands [1]. It may be present in healthy individuals, but certain phenotypic features such as deep, inflammatory cracks with trunk predominance should outweigh possible underlying neoplasia. The association between AE and hemopathies is already described, especially in non-Hodgkin lymphoma [2]. The association with classic Hodgkin lymphoma is rarer. Skin manifestations are present in 17%–53% of patients with classic Hodgkin lymphoma, mainly characterized by non-specific lesions, and can be the disease's gateway [3]. The most frequent skin manifestation is pruritus (20% of cases). Other manifestations include polymorphic skin symptoms, such as prurigo, paraneoplastic pemphigus, erythema multiforme, erythema nodosum, and various kinds of eruptions (bullous, eczematous, and psoriatic). Clinicians should recognize AE by its presentation and be aware that it may reveal Hodgkin lymphoma, especially in older patients.
The authors declare no conflict of interest.
No funding has been
Chronic myeloid leukaemia (CML) has been classically described as a disease restricted to the bone marrow with very few reports of extramedullary involvement. CNS involvement with CML has been described in the literature as an aggressive disease in the leukaemic phase either preceding or coexisting with medullary blast crisis or seen in patients with long-term Imatinib therapy. No treatment consensus exists for this patient group and outcomes remain poor. We hereby present a very rare report of CNS involvement with chronic phase CML at diagnosis in a patient who presented with raised intracranial pressure and cranial nerve palsies.
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