A 54-year-old male patient with acute lymphoblastic leukemia was referred to the Department of Oral Medicine. He had a primary refractory disease and was treated according to HOVON71 and HAM ...protocol. Sixteen days after the start of the HAM protocol the patient developed palatal dark red/brownish lesion and maxillary vestibular exophytic lesion. Biopsy specimens from oral lesions were taken and microbiologic evaluation confirmed the presence of
Aspergillus fumigatus
and
Rhizopus genus
. The treatment of the patient consisted of the inferior maxillectomy and intravenous posaconazole and amphotericine B for the following 28 days. Since the coinfection with
Aspergillus
and
Rhizopus
is extremely rarely seen in the oral cavity, a diagnostic and therapeutic dilemma easily presents itself.
Background
Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to ...increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published.
Aims
To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP.
Methods
We identified 26 patients treated with eBEACOPP for newly diagnosed high‐risk advanced‐stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross‐sectional study; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination.
Results
Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01).
Conclusion
The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.
Purpose
Dose‐adjusted EPOCH and rituximab (DA‐EPOCH‐R) is a regimen used for the treatment of high‐risk diffuse large B‐cell lymphoma (DLBCL) designed to overcome resistance to standard R‐CHOP by ...combining prolonged exposure of lymphoma cells to cytotoxic agents and dose‐adjustment based on toxicity. Data on outcomes of older patients are scarce.
Patients and Methods
We collected data on patients with newly diagnosed high‐risk DLBCL older than 60 years treated with DA‐EPOCH‐R. High‐risk patients were defined by the age‐adjusted international prognostic index score 2 or 3.
Results
A total of 120 patients were included. Median age was 69 years (range 60–82). Response rate was 74%; with 59% complete responses. Dose of DA‐EPOCH‐R was escalated in 50 patients (42%). Three‐year progression‐free survival (PFS) and overall survival (OS) was 53% and 58%, respectively, with treatment‐related mortality (TRM) of 13%. In univariate analysis, favorable prognostic factors were performance status (PS) (0–2 vs. 3–4), age (<70 vs. ≥70 years), and center. In multivariate analysis, PS and center retained prognostic significance. Patients with PS 0–2 had 3‐year PFS and OS of 58% and 64%, respectively, with TRM of 6%.
Conclusion
DA‐EPOCH‐R is efficacious in sufficiently fit older high‐risk DLBCL patients. Patients with poor PS have unacceptable toxicity and require less intensive therapy.
Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are ...conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (
= 0.0078) and those treated with purine analogues (
= 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (
= 0.012), especially obinutuzumab, and purine analogues (
= 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies.
Data on outcome of patients with mantle cell lymphoma (MCL) and COVID‐19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real‐world ...information about treatments and disease courses. During the COVID‐19 pandemic, additional data on MCL patients with COVID‐19 infection were collected, aiming to identify risk factors for mortality from COVID‐19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44–84) in 9 countries with evidence of a COVID‐19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.
Obinutuzumab (G) has become part of front‐line treatment of follicular lymphoma (FL) based on results of a large randomized study. Data on patients treated outside of clinical trials are lacking. We ...have retrospectively investigated efficacy and safety of G‐based immunochemotherapy regimens in 114 patients treated in a real‐life setting during a period of 2 years, largely coinciding with the COVID‐19 pandemic. The response rate was 93.8%; 18‐months overall (OS) and progression‐free survival (PFS) were 88% and 84%, respectively. Patients treated with G‐cyclophosphamide, vincristine and glucocorticoid + doxorubicine (CHOP) had statistically significantly superior OS and PFS compared to patients treated with G‐bendamustine (G‐B) (P = 0.002 and P = 0.006, respectively) due to an increase in lethal infections, most notably COVID‐19, in the latter group. A total of 12 patients died during follow‐up; 9 of 61 treated with G‐B, 1 of 49 treated with G‐CHOP and 2 of 4 treated with G‐cyclophosphamide, vincristine and glucocorticoid (CVP). SARS‐CoV‐2 infection was diagnosed in 20 (17.5%) patients. All of the 7 treated with G‐CHOP recovered, while 4 of 12 treated with G‐B died. Immunoglobulin levels and severity of neutropenia were similar between the groups. In multivariate analysis, G‐B in comparison to G‐CHOP was an independent prognostic factor (P = 0.044, hazard ratio = 9.81) after adjustment for age, sex and Follicular Lymphoma International Prognostic Index (FLIPI). Based on our experience G has excellent antilymphoma activity in patients receiving front‐line treatment for FL in real‐life setting, but during the COVID‐19 pandemic, it should be preferentially combined with CHOP, at least in patients younger than 65.
Purpose
Data on efficacy and toxicity of infradiaphragmal radiotherapy fields in lymphoma patients are scarce. We therefore performed this retrospective study to analyse our experience with ...radiotherapy exclusively to infradiaphragmal fields.
Materials and methods
we retrospectively evaluated 101 patients treated between 2003 and 2014. Median dose was 36 Gy, range 4 to 54 Gy. Medium dose per fraction was 2 Gy, range 1.5 to 7 Gy.
Results
After a median follow-up of 66 months (range 1–211 months), we observed lymphoma recurrence in 38 patients (38%), five in the RT field and 33 out-of-field. Recurrences were significantly more frequent in the salvage group (17 out-of-field and 4 in-field in 31 patients) than in adjuvant group (16 out-of-field and 1 in-field in 70 patients;
p
< 0.001).
The 2-, 5- and 10-year event-free survival (EFS) rates were 62%, 56% and 54%. The 2-, 5- and 10-year overall survival (OS) rates for the entire group of patients are 73%, 60% and 54%, respectively. Acute side effects occurred in 43 (43%) patients, most frequent gastrointestinal in 26 (26%) patients. Late side effects occurred in 12 (12%) of all patients, 6 of 23 (26%) followed up for more than 10 years. Six patients developed secondary cancers, four gastrointestinal disturbances, two diabetes mellitus and three renal failure.
Conclusion
Radiotherapy is an effective and safe treatment option for patients with infradiaphragmatic lymphoma providing excellent local disease control with minimal late toxicity. Infradiaphragmatic lymphoma localization should not be regarded as a contraindication for use of radiotherapy. However, patients should be monitored for a secondary malignancy.
Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate ...humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin’s lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.
Daratumumab je prvo monoklonsko protutijelo anti-CD38 koje se primjenjuje u liječenju multiplog mijeloma. Njegova primjena uzrokuje panreaktivnost u testovima prijetransfuzijskog ispitivanja. ...Panreaktivnost je posljedica vezanja monoklonskog protutijela anti-CD38 na protein CD38 na površini eritrocita, što u standardnom testiranju onemogućuje otkrivanje antieritrocitnih aloprotutijela i osiguranje podudarne krvi za transfuzijsko liječenje. Cilj rada bila je retrospektivna analiza vlastitih iskustava u rješavanju smetnja prijetransfuzijskog ispitivanja uzrokovanih monoklonskim protutijelom anti-CD38 i u transfuzijskom liječenju tih bolesnika. Prikazani su postupci za prijetransfuzijsko ispitivanje i transfuzijsko liječenje bolesnika liječenih monoklonskim protutijelom anti-CD38 koji su provedeni u Kliničkome bolničkom centru Zagreb. U istraživanju je analizirano 10-ero bolesnika liječenih daratumumabom. Prije i poslije primjene daratumumaba pretražena su antieritrocitna protutijela i određen je direktan antiglobulinski test. Pri transfuzijskom liječenju napravljeni su test pretraživanja antieritrocitnih protutijela i križne reakcije standardnim testiranjem i specifičnim postupcima imunohematoloških ispitivanja za uklanjanje smetnja monoklonskog protutijela anti-CD38. Postupci su uključivali obradu eritrocita ditiotreitolom koncentracije 0,2 M i neutralizacijski test uz primjenu reagensa DaraEx. Kod svih bolesnika testovi pretraživanja antieritrocitnih protutijela i križne reakcije bili su nakon primjene daratumumaba pozitivni, dok je direktan antiglobulinski test zbog primjene daratumumaba bio pozitivan u gotovo polovine bolesnika. Nakon obrade eritrocita ditiotreitolom 0,2 M učestalost lažno pozitivnih rezultata testova pretraživanja antieritrocitnih protutijela i križnih reakcija iznosila je oko 40%, a poslije primjene reagensa DaraEx oko 20%. Oba specifična postupka, obrada eritrocita ditiotreitolom 0,2 M i neutralizacijski test primjenom reagensa DaraEx, nisu se pokazala dovoljno pouzdanima u rješavanju smetnja uzrokovanih monoklonskim protutijelom anti-CD38. Zato je za transfuzijsko liječenje tih bolesnika nužno osigurati eritrocitne pripravke podudarne prema klinički najvažnijim antigenima u sustavima krvnih grupa Rh, Kell, Kidd, Duffy i MNS. Dobra suradnja između odjela i transfuzijske službe te postojanje protokola za prijetransfuzijsko ispitivanje i transfuzijsko liječenje ostaju preduvjet za pravodobno i sigurno transfuzijsko liječenje te skupine bolesnika.
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