Treatment pathways and clinical outcomes in Hodgkin lymphoma outside Europe and North America: results from the international, multicenter, retrospective, B-HOLISTIC study.

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB-IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9-20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum.Clinical trial registration: NCT03327571.

18f-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients

ABSTRACT Background: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. Objective: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. Methods: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI) was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. Results: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. Conclusions: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis.

Linfomas en la era COVID-19 / Lymphoma and COVID-19

Resumen El coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) y su traducción clínica, la enfermedad por coronavirus 2019 (COVID-19), representan una enfermedad con manifestaciones respiratorias potencialmente fatales. Actualmente existen aproximadamente 12,700,000 personas afectadas por esta virus, el cual ha ocasionado 561,517 muertes en el mundo. Los pacientes con diagnóstico de linfoma, al igual que otros pacientes con cáncer activo, presentan compromiso inmunitario, ya sea por su propia patología o debido al tratamiento que reciben, por lo que son especialmente susceptibles a desarrollar cuadros graves de COVID-19. La transmisión comunitaria del SARS-CoV-2 dificulta el acceso al sistema de salud y, por ende, el seguimiento estricto que requieren lo pacientes bajo tratamiento oncológico. En la etapa en la que nos encontramos actualmente, la transmisión global de la infección por SARS-CoV-2 continúa en ascenso, por lo que un control epidemiológico cercano es poco probable. Ante este contexto, surge la necesidad de establecer guías de tratamiento de pacientes con neoplasias hematológicas.

Abstract The SARS-CoV-2 virus and its clinical translation COVID-19 represent a disease with potentially fatal respiratory manifestations. Currently, there are approximately 12,700,000 people affected by this virus, which has caused 561,517 deaths worldwide. Patients with a diagnosis of lymphoma, like other patients with active cancer, have immune compromise either due to their own pathology or due to the treatment they receive, making them especially susceptible to developing severe cases of COVID-19. The community transmission of SARS-CoV-2 hinders access to the health system and, therefore, the strict monitoring required by patients undergoing cancer treatment. At the stage we are currently in, global transmission of SARS-CoV-2 infection continues to rise, making close epidemiological control unlikely. In this context, the need arises to establish guidelines for the treatment of patients with hematological malignancies.

18f-Fluorodeoxyglucose Positron Emission Tomography Versus Bone Marrow Biopsy for the Evaluation of Bone Marrow Infiltration in Newly Diagnosed Lymphoma Patients.

BACKGROUND: Bone marrow evaluation (BME) is crucial for establishing an accurate staging and prognosis in lymphoma patients. OBJECTIVE: The objective of the study was to study the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) against bone marrow biopsy (BMB) for BME. METHODS: Five hundred patient files of newly diagnosed lymphoma patients treated at an academic medical center were reviewed for BME at diagnosis by BMB and FDG PET-CT. Diagnostic performance of FDG PET-CT for detecting bone marrow infiltration (BMI)was assessed, as well as clinical predictors for positive BMB and positive FDG PET-CT. RESULTS: BMB was positive in 16.3% of all patients, and 28.7% had a positive FDG PET-CT for BMI. Overall, the sensitivity of FDG PET-CT was 74.1% and specificity 80.1%. As for predictors for BMB and FDG PET-CT positivity, B symptoms and thrombocytopenia were independent factors for BMI. Seventy-four patients had discordant results between BMB and FDG PET-CT, non-Hodgkin lymphoma (NHL) having the most significant discordance. This discrepancy did not affect treatment. CONCLUSIONS: FDG PET-CT shows excellent performance for the detection of BMI in Hodgkin lymphoma. For diffuse large B-cell lymphoma, we recommend performing BMB and FDG PET-CT as complementary tests. In all other NHL, a unilateral BMB is mandatory at diagnosis.

Patients' quality of life: Validation of the functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) instrument for the Mexican population.

OBJECTIVE: The functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) is a widely used instrument to assess quality of life (QOL) in hematopoietic stem cell transplant (HSCT) patients, but there is little evidence of its validity in Latin American populations. This study evaluated the psychometric properties of the Spanish language version of the FACT-BMT in Mexican patients. METHOD: First, the original version was piloted with 15 HSCT patients to obtain an adequate cultural version, resulting in the adaptation of one item. After that, the new version was completed by 139 HSCT patients. RESULTS: The results showed a FACT factor structure that explains 70.84% of the total variance, a factor structure similar to the original FACT structure, and with a high internal consistency (Cronbach's alpha = 0.867). For the BMT subscale, the best factor structure included 17 items which explain 61.65% of the total variance with an adequate internal consistency (Cronbach's alpha = 0.696). SIGNIFICANCE OF THE RESULTS: The FACT-BMT was found to be a valid and reliable instrument to evaluate QOL in Mexican patients. Our results constitute new FACT-BMT empirical evidence that supports its clinical and research uses.

A multicenter, open-label, noncomparative screening study of enzastaurin in adult patients with non-Hodgkin lymphomas.

PURPOSE: To assess the antitumor activity of enzastaurin in patients with non-Hodgkin lymphomas: T-cell lymphoma (n = 23): cutaneous and peripheral T-cell lymphoma; indolent B-cell lymphomas (n = 19): small lymphocytic, follicular grade 1 or 2, marginal zone lymphomas; and aggressive B-cell lymphomas (n = 15): follicular lymphomas grade 3, aggressive lymphoma with a clinical history. The primary objective was to determine overall tumor response. Secondary objectives included duration of response and safety. MATERIALS AND METHODS: In this multicenter, open-label, noncomparative, screening study conducted between December 2007 and February 2009, patients (≥ 18 years) who relapsed after ≥ 1 prior systemic treatment or who were intolerant to standard systemic therapy received 250 mg oral enzastaurin (125 mg tablets twice a day; a 1125-mg loading dose on day 1), in 28-day cycles for up to 2 years unless unacceptable toxicity or progressive disease occurred. RESULTS: Responses were seen in follicular lymphomas grade 3 (1/5, 20.0%), cutaneous T-cell lymphoma (2/11, 18.2%), small lymphocytic lymphomas (1/7, 14.3%), and aggressive lymphoma with a clinical history (1/10, 10.0%) in this heavily pretreated patient population (median prior therapies range from 4 to 10). Most drug-related toxicities were grade 1/2, the most common being diarrhea, peripheral edema, and pruritus. CONCLUSIONS: Enzastaurin was well tolerated but demonstrated modest responses across subgroups in this heavily pretreated patient population.

[National guidelines of diagnosis and treatment of the non-Hodgkin lymphoma]. / Guías nacionales de diagnóstico y tratamiento de linfoma no Hodgkin.

Non-Hodgkin lymphoma comprises a heterogeneous group of haematological malignancies, classified according to their clinic, anatomic-pathological features and, lately, to their molecular biomarkers. Despite the therapeutic advances, nearly half of the patients will die because of this disease. The new diagnostic tools have been the cornerstone to design recent therapy targets, which must be included in the current treatment guidelines of this sort of neoplasms by means of clinical trials and evidence-based medicine. In the face of poor diagnoses devices in most of the Mexican hospitals, we recommend the present diagnose stratification, and treatment guidelines for non-Hodgkin lymphoma, based on evidence. They include the latest and most innovative therapeutic approaches, as well as specific recommendations for hospitals with limited framework and therapy resources.

Hialohifomicosis esplénica. Comunicación de un caso / Splenic hyalohyphomycosis. Case report

La aspergilosis invasora es una causa importante de morbilidad y mortalidad en pacientes gravemente inmunodeficientes, especialmente en aquellos con neutropenia o receptores de trasplante de médula ósea o de órganos sólidos. Informamos sobre una hialohifomicosis esplénica morfológicamente sugestiva de ser causada por Aspergillus spp. en un paciente de 22 años de edad con anemia aplásica, tratado con múltiples transfusiones y antibióticos de amplio espectro(AU)

Invasive aspergillosis is an important cause of morbidity and mortality in severely immunocompromised patients, especially those who are neutropenic or who have undergone bone marrow or solid-organ transplant. We report a case of hyalohyphomycosis morphologically suggestive of an Aspergillus spp. in a 22-year-old patient with aplastic anaemia, treated with multiple transfusions and broad spectrum antibiotics(AU)

[Splenic hyalohyphomycosis. Case report]. / Hialohifomicosis esplénica. Comunicación de un caso.

Invasive aspergillosis is an important cause of morbidity and mortality in severely immunocompromised patients, especially those who are neutropenic or who have undergone bone marrow or solid-organ transplant. We report a case of hyalohyphomycosis morphologically suggestive of an Aspergillus spp. in a 22-year-old patient with aplastic anaemia, treated with multiple transfusions and broad spectrum antibiotics.

[Clinical and pathological features of Castleman's disease: experience at the Instituto Nacional de Cancerología, Mexico City]. / Características clinicopatológicas de la enfermedad de Castleman. Experiencia en el Instituto Nacional de Cancerología.

BACKGROUND: Castleman's disease (CD) is a rare, poorly understood pathological entity. We report our experience with this clinicopathological entity. METHODS: We retrospectively analyzed records of all patients with CD from 1996 to 2003. The disease was classified as unicentric if a solitary mass was present or multicentric if generalized lymphadenopathy was present. We further subdivided the disease into hyaline vascular (HV) and plasma cell (PC) histological variants. RESULTS: We found 11 patients with CD. Six patients had unicentric disease and five had multicentric disease. Median follow-up was 40 months. All patients with unicentric disease had the HV variant. Of the five patients with multicentric disease, four had the PC variant and one had the HV. Five patients with unicentric disease were treated surgically with complete resection, and only one patient was treated with chemotherapy. All remain alive without disease. Three patients with multicentric disease were treated with chemotherapy, and two patients received chemotherapy plus radiotherapy for residual disease. Two patients received second-line chemotherapy with a favorable outcome. Two patients with a comorbid condition had a poor outcome. CONCLUSIONS: Clinical characteristics, pathological features and treatment results are similar to that reported in other populations.

[Histiocytic sarcoma of the small intestine: Report of one case]. / Sarcoma histiocítico de intestino delgado: Reporte de un caso y revisión de la literatura.

Histiocytic sarcoma (HS) is a rare malignant neoplasm of the lymphohematopoietic system, that occurs in lymph nodes, skin and at extranodal sites, particularly the gastrointestinal tract. Although it shows characteristics histological and immunohistochemical features, it may be misdiagnosed. We report a 67 year-old female patient presenting with colicky abdominal pain and vomiting. A CT scan of the abdomen revealed a tumor in the ileum, that was surgically removed. On pathology, the neoplastic cells displayed large abundant eosinophilic cytoplasm, with bizarre-shaped nuclei, that expressed CD 45, CD 68 and lisozyme. The diagnosis of HS requires the use of a panel of immunohistochemical markers and may be supported by ultrastructural findings.

Características clinicopatológicas de la enfermedad de Castleman: experiencia en el Instituto Nacional de Cancerología / Clinical and pathological features of Castleman's disease: experience at the Instituto Nacional de Cancerología, Mexico City

Introducción: La enfermedad de Castleman es una entidad patológica poco comprendida, descrita originalmente en pacientes europeos. Informamos nuestra experiencia con esta entidad clinicopatológica en pacientes del Instituto Nacional de Cancerología de la Ciudad de México. Material y métodos: Analizamos retrospectivamente los expedientes de pacientes con enfermedad de Castleman de 1996 a 2003. La enfermedad fue monocéntrica si había solo un ganglio o multicéntrica si se encontraba linfoadenopatía generalizada. Además, se dividió en las variantes histológicas hialinovascular y de células plasmáticas. Resultados: Once pacientes con enfermedad de Castleman fueron diagnosticados en el periodo referido, seis tenían enfermedad monocéntrica y cinco multicéntrica. La mediana de seguimiento fue de 40 meses. Todos los pacientes con enfermedad monocéntrica tenían la variante hialinovascular. De los cinco con multicéntrica, cuatro tenían la variante de células plasmáticas y uno la hialinovascular. Cinco pacientes con enfermedad monocéntrica se trataron con cirugía y uno con quimioterapia; al momento de este informe todos permanecían vivos y sin enfermedad. Tres pacientes con enfermedad multicéntrica recibieron quimioterapia y dos, quimioterapia más radioterapia por enfermedad residual; a dos pacientes se les prescribió quimioterapia de segunda línea, con buena respuesta. Dos pacientes con una condición asociada evolucionaron desfavorablemente. Conclusiones: Las características clínicas, patológicas y los resultados del tratamiento son similares a los señalados en otras poblaciones.

BACKGROUND: Castleman's disease (CD) is a rare, poorly understood pathological entity. We report our experience with this clinicopathological entity. METHODS: We retrospectively analyzed records of all patients with CD from 1996 to 2003. The disease was classified as unicentric if a solitary mass was present or multicentric if generalized lymphadenopathy was present. We further subdivided the disease into hyaline vascular (HV) and plasma cell (PC) histological variants. RESULTS: We found 11 patients with CD. Six patients had unicentric disease and five had multicentric disease. Median follow-up was 40 months. All patients with unicentric disease had the HV variant. Of the five patients with multicentric disease, four had the PC variant and one had the HV. Five patients with unicentric disease were treated surgically with complete resection, and only one patient was treated with chemotherapy. All remain alive without disease. Three patients with multicentric disease were treated with chemotherapy, and two patients received chemotherapy plus radiotherapy for residual disease. Two patients received second-line chemotherapy with a favorable outcome. Two patients with a comorbid condition had a poor outcome. CONCLUSIONS: Clinical characteristics, pathological features and treatment results are similar to that reported in other populations.

Primary lymphomas of the breast: a report on 5 cases studied in a period of 5 years at the Hospital General de México.

Breast lymphomas can be primary or secondary. Among the primary lymphomas, the most common histologic types are the large B-cell diffuse lymphomas and the extranodal B mucosa-associated lymphatic tissue lymphomas. We studied 5 cases of primary breast lymphoma in female patients. The criteria for the diagnosis were based on the proposal of Wiseman and Liao: (1) in the biopsy or surgical specimen, the lymphoma involves the breast parenchyma, and (2) nonsystemic disease at diagnosis. Clinical data, histologic findings, immunohistochemical reactions, treatment, and clinical follow-up were reviewed. The 5 patients were young women with average age of 27 years; the youngest was 20 years old, and the oldest was 44 years old. The right breast was the most affected, and 1 patient was HIV positive. The most common symptoms were the presence of nodes, progressive increase of volume, collateral venous network, and hemorrhagic discharge from the nipple. The clinical course was of 1 to 14 months before diagnosis. Three patients died because of central nervous system infiltration, one is still alive, and the other was lost during follow-up. Histologically, all primary breast lymphomas were large B-cell lymphomas; one had focal starry sky pattern, and the other 3 were centroblastic. All were positive to CD20 and CD79(a), 3 expressed bcl2, and 2 expressed bcl6. The proliferation index was between 60% and 80%. Primary breast lymphomas are rare. The average age of our patients was 27 years, and their clinical course was aggressive with central nervous system infiltration. The most common histologic type was the large B-cell diffuse lymphoma. Differential diagnosis must be established in the presence of poorly differentiated lobules and ductal carcinoma.

Sarcoma histiocítico de intestino delgado: Reporte de un caso y revisión de la literatura / Histiocytic sarcoma of the small intestine: Report of one case

Histiocytic sarcoma (HS) is a rare malignant neoplasm of the lymphohematopoietic system, that occurs in lymph nodes, skin and at extranodal sites, particularly the gastrointestinal tract. Although it shows characteristics histoiogical and immunohistochemical features, it may be misdiagnosed. We report a 67 year-old female patient presenting with colicky abdominal pain and vomiting. A CT sean of the abdomen revealed a tumor in the ileum, that was surgically removed. On pathology, the neoplastic cells displayed large abundant eosinophilic cytoplasm, with bizarre-shaped nuclei, that expressed CD 45, CD 68 and lisozyme. The diagnosis of HS requires the use of a panel of immunohistochemical markers and may be supported by ultrastructural findings .

Allografting in patients with severe, refractory aplastic anemia using peripheral blood stem cells and a fludarabine-based conditioning regimen: the Mexican experience.

We studied the effectiveness of a fludarabine/cyclophosphamide-based conditioning regimen without anti-thymocyte globulin in 23 aplastic anemia patients who had no response to previous conventional pharmacologic treatment. Patients received oral busulphan 4 mg/kg/day/2 days, IV cyclophosphamide 350 mg/m(2)/day/3 days, and fludarabine 30 mg/m(2)/day/3 days. For GVHD prophylaxis, patients received MTX 5 mg/m(2) days +1, +3, +6, and +11 and oral cyclosporin A (CyA) 5 mg/kg/day, starting on day -1. Peripheral blood stem cell products were used with a median dose of 5.5 x 10(6) CD34(+)/kg. The patients were followed for an average of 25 months. By a median of day +11, an ANC > 0.5 x 10(9)/L was reached; and by day +12, the platelet count had reached >20,000 x 10(9)/L. Acute grade I-II GVHD occurred in 4 patients, whereas limited chronic GVHD presented in 6 cases. Twenty-one patients (91.3%) achieved engraftment. Two patients failed to engraft, and 4 developed late rejection; 2 of these individuals died, 2 have survived with high transfusion requirements, whereas 2 received a second peripheral blood stem cell infusion and achieved sustained engraftment. Currently 21 (91%) of the 23 patients are alive, whereas 19 of 21 (90%) remain in complete remission. The average cost was about USD 15,000 for this kind of reduced-intensity allotransplant. Reduced-intensity stem cell transplantation represents an affordable alternative to traditional more cytotoxic conditioning for severe aplastic anemia (SAA) patients. Long-term effects however, remain to be evaluated.

Allogeneic peripheral blood stem cell transplantation. Safety, hematologic recovery, kinetics, and complications.

BACKGROUND: Hematopoietic stem cell transplants are an accepted treatment for several malignant and nonmalignant hematologic diseases. Recently, the peripheral blood, after mobilization of stem cells with growth factors, has become the source of choice for hematopoietic stem cells. We report on a series of patients who received peripheral blood stem cell transplants at the Instituto Nacional de Cancerologia (INCAN) in Mexico City. METHODS: Between May 1995 and December 1999, 33 patients received peripheral blood stem cell transplants to treat hematologic diseases. Sixty percent of our patients had chronic myelocytic leukemia (CML). All had a matched related donor. Patients were conditioned with one of five different conditioning regimens and subsequently received one of two different graft-vs.-host disease prophylaxis regimens. Stratified Wilcoxon rank-sum, chi square, and Mann-Whitney tests were used to analyze the results. RESULTS: In our series, median time to achieve a total neutrophil count of 0.5 x 10(9)/L was 14 days and to achieve a platelet count of 20 x 10(9)/L, 15 days. Acute graft-vs.-host disease occurred in seven patients. Chronic graft-vs.-host disease occurred in 69% of surviving patients. Survival for low-risk patients was 67% and for the high-risk group, 9%. CONCLUSIONS: Peripheral blood stem cells produce a faster hematopoietic recovery. The rate of acute graft-vs.-host disease is not increased using the peripheral blood as source of stem cells; however, chronic graft-vs.-host disease continues to be a significant problem. Donors tolerated the procurement procedure without complications.