Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around textured-surface breast implants. In a subset of patients, this disease can ...involve surrounding tissues, spread to regional lymph nodes, and rarely metastasize to distant sites. The aim of this study was to assess sequential pathologic specimens from patients with breast implant-associated ALCL to better understand the natural history of early-stage disease. To achieve this goal, we searched our files for patients who had breast implant-associated ALCL and who had undergone earlier surgical intervention with assessment of biopsy or cytologic specimens. We then focused on the patient subset in whom a definitive diagnosis was not established, and patients did not receive current standard-of-care therapy at that time. We identified a study group of ten patients with breast implant-associated ALCL in whom pathologic specimens were collected 0.5 to 4 years before a definitive diagnosis was established. A comparison of these serial biopsy specimens showed persistent disease without change in pathologic stage in three patients, progression in five patients, and persistence versus progression in two patients. Eventually, six patients underwent implant removal with complete capsulectomy and four underwent partial capsulectomy. Seven patients also received chemotherapy because of invasive disease, three of whom also received radiation therapy, two brentuximab vedotin after chemotherapy failure, and one allogeneic stem cell transplant. Eight patients achieved complete remission and two had partial remission after definitive therapy. At time of last follow-up, six patients were alive without disease, one had evidence of disease, one died of disease, and two patients died of unrelated cancers. In summary, this analysis of sequential specimens from patients with breast implant-associated ALCL suggests these neoplasms persist or progress over time if not treated with standard-of-care therapy.
TP53 deletion (ΔTP53) in myeloma is known to be a high-risk finding associated with poorer prognosis. The prognostic impact of underlying cytogenetic heterogeneity in patients with myeloma associated ...with ΔTP53 is unknown. We studied 90 patients with myeloma associated with ΔTP53 identified by interphase fluorescence in situ hybridization and assessed the impact of karyotype and coexisting alterations of IGH, RB1, and CKS1B. There were 54 men and 36 women with a median age of 59 years (range 38-84); 14 patients had a normal karyotype (NK/ΔTP53), 73 had a complex karyotype (CK/ΔTP53), and 3 had a non-complex abnormal karyotype. Patients with CK/ΔTP53 showed a significantly poorer overall survival compared with patients with NK/ΔTP53 (P=0.0243). Furthermore, in the CK/ΔTP53 group, patients with IGH rearrangement other than t(11;14)(q13;q32)/CCND1-IGH, designated as adverse-IGH, had an even worse outcome (P=0.0045). In contrast, RB1 deletion, CKS1B gain, ploidy, additional chromosome 17 abnormalities, or ΔTP53 clone size did not impact prognosis. Stem cell transplant did not improve overall survival in either the NK/ΔTP53 or CK/ΔTP53 (P=0.8810 and P=0.1006) groups, but tandem stem cell transplant did improve the overall survival of patients with CK/ΔTP53 (P=0.0067). Multivariate analysis confirmed in this cohort that complex karyotype (hazard ratio 1.976, 95% CI 1.022-3.821, P=0.043), adverse-IGH (hazard ratio 3.126, 95% CI 1.192-8.196, P=0.020), and tandem stem cell transplant independently correlate with overall survival (hazard ratio 0.281, 95% CI 0.091-0.866, P=0.027). We conclude that comprehensive genetic assessment adds to TP53 status in the risk stratification of myeloma patients.
Multiple myeloma is cytogenetically heterogeneous and a hyperdiploid karyotype is considered currently to have standard risk. In this study, we investigated the clinical impact of ...additional–structural–chromosomal aberrations assessed by chromosome analysis in 284 patients with a hyperdiploid karyotype that were subdivided into four groups based on the complexity of additional–structural–chromosomal aberrations: group 1, no additional–structural–chromosomal aberrations (n=35); group 2, one additional–structural–chromosomal aberration (n=46); group 3, two additional–structural–chromosomal aberrations (n=39); group 4, ≥three additional–structural–chromosomal aberrations (n=164). Clinicopathological data among these groups showed no differences, except patients in group 1 had higher hemoglobin (P=0.031) and albumin (P=0.045) levels. The median follow-up was 55 months (range, 3–221). The median overall survival of patients in groups 1–4 was negatively correlated with the number of the additional–structural–chromosomal aberrations: 98, 76, 61, and 48 months, respectively (P<0.0001). In group 4, CKS1B gain, RB1, or TP53 deletions had no additional impact on overall survival; however, trisomy 3 or 15 conferred a much better overall survival, and monosomy 13 and 14 predicted a worse outcome. In addition, the overall survival of patients in groups 3 and 4 was similar to a subset of high-risk multiple myeloma cases (n=21) (P=0.387). About 192 (67.6%) patients who received stem cell transplantation did not show improved overall survival compared with non-stem cell transplantation patients (n=92; P=0.142) overall; however, they did show significantly improved overall survival in patients with refractory disease in group 4 (P=0.0084). Multivariate analysis showed that two or more additional–structural–chromosomal aberrations (P<0.0001), stages (P=0.02 and P=0.002) and relapsed disease (P=0.009) negatively impacted the overall survival. We conclude that hyperdiploid karyotypes in multiple myeloma are associated with additional–structural–chromosomal aberrations and a greater number of additional–structural–chromosomal aberrations predicts poorer clinical outcome. A hyperdiploid karyotype with ≥2 additional–structural–chromosomal aberrations at chromosomal level should be considered an independent high-risk factor.
Introduction: Cytogenetic abnormalities can be detected in about 20% of patients with polycythemia vera (PV) at initial diagnosis. The accumulated risk for acute myeloid leukemia (AML) transformation ...from PV has been estimated to be 2.3-14.4% at 10 years. Risk factors for AML transformation suggested in other studies include older age, abnormal karyotype and high leukocyte count. The purpose of this study is to evaluate the association of cytogenetic abnormalities with AML transformation in PV.
Methods: We searched the database at our institution for patients with a diagnosis of PV during Jan. 1994 to Apr. 2015. Demographic data, clinical presentations and follow-up, and laboratory data including karyotype before and after AML transformation were collected. Bone marrow morphology, especially evidence of myelodysplasia, myelofibrosis and blast percentage were evaluated.
Results: A total of 317 patients with a diagnosis of PV were identified. 36 (11%) patients progressed to AML (Group A), including 15 who presented in chronic phase and 21 in blast phase. The median interval from the diagnosis of PV to AML transformation was 97 months (range, 11 - 331 months). For comparison, 50 patients with similar demographic features during the same time interval but no evidence of AML transformation were also included in the study (Group B). The age of patients in both groups was comparable (median age: 57 vs. 54 years, p=0.2791). All patients were positive for JAK2 V617F mutation. The main therapies for patients with chronic phase PV included phlebotomy, hydrea, and tyrosine kinase inhibitors in a small subset of patients. There was no significant difference of treatments among the patients in groups A and B.
Karyotype at chronic phase of PV was available in 15 patients in Group A and all 50 patients in Group B. Eleven (73%) patients in Group A showed an abnormal karyotype in chronic phase. The most common chromosomal abnormalities were trisomy 1q (n=6, 40%), including 4 (27%) patients with +1, der(1;7)(q10;p10) resulting in trisomy 1q and del(7q); and complex karyotype (n=3, 20%). Del(20q) and +8 was uncommon, only detected in 1 patient each. In Group B, 11 (22%) patients had an abnormal karyotype, which was much less frequent compared with Group A. No patients in Group B showed a complex karyotype or trisomy 1q; instead, del(20q) (n=6, 55%), +9 and/or +8 (n=5, 45%) were the most common chromosomes abnormalities detected.
The median follow-up was 10 years in Group A and 14.5 years in Group B. At the time of AML transformation, 35 (97%) patients in Group A showed an abnormal karyotype, including 21 (58%) patients with a complex karyotype, 22 patients with -5/del(5q) and/or -7/del(7q) and 10 (28%) with trisomy 1q 8 with +1, der(1;7). Among the 15 patients who had karyotypic information during the chronic phase, 4 (27%) patients showed clonal evolution and 7 (47%) acquired new unrelated abnormal clones when AML transformation occurred.
Morphologically, 15 patients in Group A had sequential bone marrow evaluation from chronic phase to blast phase, 14 (93%) patients developed myelofibrosis and 7 (47%) patients showed multilineage dysplasia during the chronic phase. At the time of AML transformation, 35 (97%) patients showed myelodysplasia. In Group B, 5 (10%) patients developed myelodysplasia and 31(62%) developed myelofibrosis in follow-up bone marrow samples.
Conclusion: Cytogenetic abnormalities are associated with AML transformation in PV patients. Patients with an abnormal karyotype, especially with abnormalities of trisomy 1q +1,der(1;7)(q10;p10) or a complex karyotype, are at highest risk to develop clonal evolution or acquire new myelodysplasia-related clones like -5/del(5q) and/or -7/del(7q) or develop myelodysplasia and transform into AML. On the other hand, cytogenetic abnormalities, such as del(20q), +8 and/or +9, although commonly detected in PV, are associated with a low risk for myelodysplasia and AML transformation. Surveillance for cytogenetic abnormalities is helpful in the risk assessment of AML transformation in PV patients.
No relevant conflicts of interest to declare.
T-cell large granular lymphocytic (T-LGL) leukemia after hematopoietic stem cell transplantation (SCT) is rare and its natural history and clinical outcome have not been well described. We report the ...clinical, morphologic, immunophenotypic, and molecular features of a case of donor-derived T-LGL leukemia in a 16-year-old man who received allogeneic SCT for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The patient presented with persistent neutropenia and splenomegaly 9 months after SCT when the chimerism study showed a 100% donor pattern. A splenectomy revealed T-LGL leukemia. Flow cytometric analysis showed an aberrant T-cell population positive for CD3, CD5 (dim, subset), CD7, CD8, CD16 (subset), CD57, CD94 (dim, partial), and T-cell receptor (TCR) αβ, and negative for CD4, CD26, CD56, and TCRγδ. Molecular studies showed monoclonal TCRβ and TCRγ gene rearrangements. Both the immunophenotype and molecular profile of the T-LGL leukemia were different from the pre-SCT PTCL. Sequencing analysis for STAT3 exon 21 did not reveal any mutation in both pre-SCT and post-SCT specimens. The patient did not receive any treatment for T-LGL leukemia; however, his count progressively increased after splenectomy, despite the presence of persistent T-LGL leukemia in the bone marrow. There was no evidence of recurrent PTCL. We propose an algorithm to diagnose this rare post-SCT neoplasm.
Las complicaciones trombóticas mayores en las neoplasias mieloproliferativas (NMP) representan un importante problema clínico debido a su elevada morbilidad, la complejidad de su manejo y su ...mortalidad asociada. La aparición de una trombosis comporta una estratificación de alto riesgo trombótico de la NMP y determina el inicio o la optimización del tratamiento citorreductor y el uso de terapia antiplaquetaria o anticoagulante como profilaxis secundaria. La incidencia de trombosis en el momento del diagnóstico es mayor que durante la evolución de la enfermedad, localizándose en territorio arterial en el 60-70% casos. Una vez se ha producido una trombosis, hasta el 20-33% de los pacientes sufre una recurrencia trombótica en el mismo territorio vascular inicial.
Control de los síntomas Martínez-Castro, Raúl; Barranco-Lampón, Gilberto; Arana-Luna, Luara L. ...
Gaceta médica de México,
03/2024, Letnik:
158, Številka:
93
Journal Article
Recenzirano
Odprti dostop
Además de la sintomatología secundaria a la esplenomegalia, a las alteraciones microvasculares y a las complicaciones trombohemorrágicas, los pacientes con neoplasias mieloproliferativas (NMP) pueden ...experimentar una importante carga sintomática atribuida a un aumento de citocinas inflamatorias circulantes. Estos síntomas pueden ser severos y limitar la calidad de vida. Por ello, además de la prevención de las complicaciones, uno de los objetivos del tratamiento de las NMP es el control de los síntomas.
Mielofibrosis: diagnóstico y tratamiento Martínez-Castro, Raúl; Barranco-Lampón, Gilberto; Arana-Luna, Luara L. ...
Gaceta médica de México,
03/2024, Letnik:
158, Številka:
93
Journal Article
Recenzirano
Odprti dostop
La mielofibrosis (MF) es una neoplasia mieloproliferativa negativa para BCR-ABL1 caracterizada por mieloproliferación clonal, señalización de cinasa desregulada y liberación de citocinas anormales. ...En los últimos años se han realizado importantes avances en el conocimiento de la biología molecular y la valoración pronóstica de la MF. El tratamiento convencional tiene un impacto limitado en la supervivencia de los pacientes; incluye un enfoque de espera para pacientes asintomáticos, agentes estimulantes de la eritropoyesis, andrógenos o agentes inmunomoduladores para la anemia, fármacos citorreductores como la hidroxiurea para la esplenomegalia y los síntomas constitucionales, y esplenectomía o radioterapia en pacientes seleccionados. El descubrimiento de la mutación Janus cinasa (JAK) 2 desencadenó el desarrollo de la terapia dirigida molecular de la MF. Los inhibidores de JAK son efectivos tanto en MF con JAK2 positivo como con JAK2 negativo; uno de ellos, el ruxolitinib, es la mejor terapia disponible actualmente para la esplenomegalia y los síntomas constitucionales de la MF. Sin embargo, aunque el ruxolitinib ha cambiado el escenario terapéutico de la MF, no hay indicios claros de un efecto modificador de la enfermedad. El alotrasplante de células madre sigue siendo la única terapia curativa de la MF, pero debido a su morbilidad y mortalidad asociadas, generalmente se restringe a pacientes elegibles con MF de riesgo alto e intermedio 2. Para mejorar los resultados terapéuticos actuales, actualmente se está probando la combinación de inhibidores de JAK con otros agentes y se están investigando fármacos más nuevos.
Objetivo: El objetivo del consenso es poner a disposición de los profesionales de las diferentes instituciones de salud pública en nuestro país, quienes se encuentran a cargo de estas enfermedades, ...la información más relevante y actualizada acerca de su diagnóstico y tratamiento en la práctica clínica. Con este consenso interinstitucional esperamos contribuir a mejorar la calidad de la atención de los pacientes con neoplasias mieloproliferativas crónicas a todo lo ancho y largo de la República Mexicana, con el fin de unificar criterios tanto en diagnóstico como en tratamiento de las diferentes enfermedades mieloproliferativas.
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