Background.
The use of gonadotropin‐releasing hormone analogs (GnRHas) for fertility preservation is not unequivocally accepted. It is controversial whether GnRHa can increase the pregnancy rate in ...survivors.
Patients and Methods.
This is a retrospective cohort study. Every patient referred for fertility preservation was offered cryopreservation of embryos, ova, and ovarian tissue and GnRHa. The patients were consecutively included. The primary outcome was spontaneous pregnancies. The secondary outcome was cyclic ovarian function (COF) versus premature ovarian failure (POF). These outcomes were assessed 2 years or more after chemotherapy.
Results.
We compared 286 patients who received gonadotropin‐releasing hormone agonist (GnRHa) with chemotherapy with 188 patients who were treated with chemotherapy alone. Ovarian function could be determined in 217 patients. Overall, 87% (127 of 146) of the patients in the GnRHa group retained COF and 13% (19 of 146) suffered POF, whereas in the control group, 49% (35 of 71) experienced COF and 51% (36 of 71) suffered POF (p = .0001). The odds ratio (OR) for preserving COF was 6.87 for the patients who received GnRHa (95% confidence interval CI 3.4–13.4). Overall 60% (112 of 188) of the survivors conceived: 69.3% (84 of 122) of the patients in the GnRHa group compared with 42.4% (28 of 66) in the control group (p = .006). In the GnRHa group, 123 healthy newborns were delivered, versus 40 in the controls. Spontaneous pregnancies occurred in 65.6% (80 of 122) of the survivors in the GnRHa group versus 37.9% (25 of 66) in the control group (p = .0004, OR 3.12, 95% CI 1.7–5.8).
Conclusion.
Adding GnRHa to chemotherapy significantly increases the OR for spontaneous conception, in addition to COF. It is suggested that GnRHa cotreatment should be added before and during gonadotoxic chemotherapy.
Implications for Practice:
The use of gonadotropin‐releasing hormone analogs (GnRHa) for fertility preservation is not unequivocally accepted and is even controversial. This study compared 286 patients who received GnRHa with chemotherapy with 188 patients who were treated with chemotherapy alone. Ovarian function could be determined in 217 patients. The odds ratio for preserving cyclic ovarian function was 6.87 for the patients who received GnRHa. Furthermore, the total and spontaneous pregnancy rate was significantly higher for those who received the agonist (p = .006). Adding GnRHa to chemotherapy significantly increased the odds ratio for spontaneous conception, in addition to preserving regular ovarian function. It is suggested that GnRHa cotreatment should be administered to young women in conjunction with gonadotoxic chemotherapy.
Patients who received gonadotropin‐releasing hormone agonist (GnRHa) with chemotherapy were compared with patients who were treated with chemotherapy alone to determine whether GnRHa can increase the pregnancy rate in survivors. The results indicated that adding GnRHa to chemotherapy significantly increases the odds ratio for spontaneous conception, in addition to cyclic ovarian function. It is suggested that GnRHa cotreatment should be added before and during gonadotoxic chemotherapy.
Background
Patients with severe B‐cell depletion related to hematological malignancies or B‐cell targeted therapy suffer from impaired antibody responses to SARS‐CoV‐2 and are at risk for prolonged ...COVID‐19. In this population, COVID‐19 convalescent plasma (CCP) may provide passive immunity, enhance immune response, and promote virus neutralization. This study evaluated outcomes of B‐cell depleted patients with persistent COVID‐19 treated with CCP.
Study Design and Methods
This analysis included all consecutive severely B‐cell depleted patients with persistent COVID‐19, receiving CCP at Rambam between 01.2022–02.2023. Persistent COVID‐19 was defined as the presence of symptoms for ≥14 days in patients with negative SARS‐CoV‐2 nucleocapsid antibody test results.
Results
Twenty patients met inclusion criteria, 17 of whom had hematological malignancies, two suffered from rheumatoid arthritis and one had both. Twelve patients received anti‐CD‐20 treatment, one ‐ CAR‐T cells and three underwent stem cell transplantation. The median duration of COVID‐19 symptoms was 27.5 days (range 14–97); 12 patients had mild‐to‐moderate COVID‐19 and 8 had severe infection. Sixteen patients required hospitalization. The majority of patients received other COVID‐19 therapies before CCP. Within a median of two days (range 1–16) post‐infusion, 19/20 patients clinically improved. No CCP‐associated adverse events were documented. COVID‐19 symptoms recurred in 3 of the improved patients. Two patients died from COVID‐19 on days 1 and 90 following the first CCP infusion.
Discussion
In severely B‐cell depleted patients with persistent COVID‐19, CCP is safe and associated with rapid clinical improvement. This subset of immunocompromised patients could particularly benefit from CCP administration.
The last 3 decades have witnessed a major evolution in the treatment of advanced-stage Hodgkin lymphoma (HL). The most prominent of these developments include the introduction of the international ...prognostic scoring (IPS) system; therapeutic decision-making based on both IPS and interim PET/CT data; the finding that a negative interim PET/CT result could be safely used for treatment de-escalation; the introduction of intensive combination chemotherapy like escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin (vincristine), procarbazine, and prednisone); and further modification of this protocol with the incorporation of a conjugated anti-CD30 antibody brentuximab vedotin (BV) into first-line regimens, like BV-AVD (BV+ adriamycin, vinblastine and dacarbazine) and BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone). The accruing data about the toxicity of the escalated BEACOPP protocol have led to decreasing the number of therapeutic cycles, substitution of toxic agents like procarbazine with dacarbazine (e.g., BEACOPDac), and reduction/omission of radiation therapy. Lately, a significant advancement has been made by the integration of checkpoint inhibitors in the first-line treatment, with preliminary results demonstrating the superiority of anti-PD1 combined with chemotherapy (nivolumab-AVD) compared to the BV-AVD regimen. This review aims to analyze recently published studies whose findings could change the treatment practice in advanced-stage HL.
Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data ...from the immunochemotherapy era are limited.
Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records.
In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15–25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate HDMTX or platinum-containing regimens), age ≤60 years, performance status 0–1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0–1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36–80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9).
In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.
•The overall prognosis of secondary CNS relapse of diffuse large B-cell lymphoma remains poor.•Few patients achieve favourable long-term outcomes with current therapies.•Younger patients with parenchymal SCNS and no systemic involvement have a relatively good prognosis after intensive therapies.•The addition of rituximab to HDMTX-based regimens seems to improve outcomes.
Patients with lymphoma, especially those treated with anti-CD20 monoclonal antibodies, suffer high COVID-19-associated morbidity and mortality. The goal of this study was to assess the ability of ...lymphoma patients to generate a sufficient humoral response after two injections of BNT162b2 Pfizer vaccine and to identify factors influencing the response. Antibody titers were measured with the SARS-CoV-2 IgG II Quant (Abbott ) assay in blood samples drawn from lymphoma patients 4 2 weeks after the second dose of vaccine. The cutoff for a positive response was set at 50 AU/mL. Positive serological responses were observed in 51% of the 162 patients enrolled in this cross-sectional study. In a multivariate analysis, an interval of <12 months between the last anti-CD20 monoclonal antibody dose and the second vaccine dose (odds ratio=31.3 95% confidence interval: 8.4-116.9, P<0.001) and presence of active lymphoma (odds ratio=4.2 (95% confidence interval: 2.1- 8.2), P=0.006) were identified as negative response predictors. The rate of seropositivity increased from 3% in patients vaccinated within 45 days after the last monoclonal antibody administration to 80% in patients vaccinated >1 year after this therapy. The latter percentage was equal to that of patients never exposed to monoclonal antibodies. In conclusion, lymphoma patients, especially those recently treated with anti- CD20 monoclonal antibodies, fail to develop sufficient humoral response to BNT162b2 vaccine. While a serological response is not the only predictor of immunity, its low level could make this population more vulnerable to COVID-19, which implies the need for a different vaccination schedule for such patients.
PET/CT with (18)F-FDG is an important noninvasive diagnostic tool for management of patients with lymphoma, and its use may surpass current guideline recommendations. The aim of the present study is ...to enlarge the growing body of evidence concerning (18)F-FDG avidity of lymphoma to provide a basis for future guidelines.
The reports from (18)F-FDG PET/CT studies performed in a single center for staging of 1,093 patients with newly diagnosed Hodgkin disease and non-Hodgkin lymphoma between 2001 and 2008 were reviewed for the presence of (18)F-FDG avidity. Of these patients, 766 patients with a histopathologic diagnosis verified according to the World Health Organization classification were included in the final analysis. (18)F-FDG avidity was defined as the presence of at least 1 focus of (18)F-FDG uptake reported as a disease site. Nonavidity was defined as disease proven by clinical examination, conventional imaging modalities, and histopathology with no (18)F-FDG uptake in any of the involved sites.
At least one (18)F-FDG-avid lymphoma site was reported for 718 patient studies (94%). Forty-eight patients (6%) had lymphoma not avid for (18)F-FDG. (18)F-FDG avidity was found in all patients (100%) with Hodgkin disease (n = 233), Burkitt lymphoma (n = 18), mantle cell lymphoma (n = 14), nodal marginal zone lymphoma (n = 8), and lymphoblastic lymphoma (n = 6). An (18)F-FDG avidity of 97% was found in patients with diffuse large B-cell lymphoma (216/222), 95% for follicular lymphoma (133/140), 85% for T-cell lymphoma (34/40), 83% for small lymphocytic lymphoma (24/29), and 55% for extranodal marginal zone lymphoma (29/53).
The present study indicated that with the exception of extranodal marginal zone lymphoma and small lymphocytic lymphoma, most lymphoma subtypes have high (18)F-FDG avidity. The cumulating evidence consistently showing high (18)F-FDG avidity in the potentially curable Burkitt, natural killer/T-cell, and anaplastic large T-cell lymphoma subtypes justifies further investigations of the utility of (18)F-FDG PET in these diseases at presentation.
Abstract Background and Objectives Spontaneous massive foetomaternal haemorrhage (SM‐FMH) is a rare yet critical condition that poses substantial risk to foetal health and survival. Existing data ...indicate that many cases may be undiagnosed. The current study aimed to investigate and validate the utility of identifying mixed field red blood cell (RBC) agglutination during maternal blood typing as a diagnostic aid for SM‐FMH. Materials and Methods Retrospective analysis of medical records from neonates born at our tertiary, university‐affiliated medical centre between 2016 and 2023 was performed. Diagnosis of SM‐FMH was based on neonates born with severe anaemia (haematocrit HCT <15%) within the first 24 h post‐delivery with positive maternal Kleihauer–Betke (KB) test. Maternal ABO/Rhesus D (RhD) blood typing results were scrutinized with the primary objective of assessing the ability to identify dual RBC populations in cases clinically diagnosed with SM‐FMH. Results Among 29,192 neonates studied, a mere 0.02% (5 cases) exhibited severe SM‐FMH. Notably, a mixed field RBC agglutination was discerned in 80% (4/5) of these cases. Conclusion This study underscores the significance of detecting mixed field RBC agglutination during antepartum maternal ABO/RhD blood typing as a potential indicator for SM‐FMH. Increased awareness among blood bank technology specialists and obstetricians regarding these laboratory findings could prove instrumental in saving foetal lives.
Measuring oxygen saturation in capillary vessels could provide valuable information on oxygen transport and tissue viability. Most spectroscopic measurement techniques, however, lack the spatial ...resolution to account for the small vessel dimensions within a scattering tissue and the steep gradients of oxygen saturation levels. Here, we developed a noninvasive technique for image-guided confocal measurement of the optical absorption spectrum from a small region that is comparable in size to the cross section of a single capillary vessel. A wide range of oxygen saturation levels were measured in a single capillary in a human volunteer, with blood deoxygenation rates of 7.1% per hundred microns. The technique could help in studying oxygen exchange dynamics in tissues and could play a key role in future clinical diagnosis and therapeutic applications that require localized functional tissue inspection.
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