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The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL), particularly the influence off previous InO response and the timing of administration. We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory (r/r) ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO-exposed). InO-exposed patients were more heavily pretreated (p= 0.02) and frequently had active marrow disease pre-apheresis (p= 0.03). Response rate and toxicity profile following brexu-cel were comparable for InO-exposed and InO-naïve; however, consolidation therapy post brexu-cel response was utilized at a higher rate in InO-naïve patients (p= 0.005). With a median follow up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS) (p=0.013) and overall survival (OS) (p=0.006) in univariate analyses; however, prior InO exposure did not influence PFS (HR 1.20, 95%CI, 0.71-2.03) in multivariate models. When InO-exposed patients were stratified according to prior InO response, InO responders had superior PFS (p=0.002) and OS (p<0.0001) relative to InO-refractory. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (p=0.51) and OS (p=0.86) for patients receiving InO as bridging therapy or pre-apheresis. In conclusion, while InO exposure was associated with inferior survival outcomes following brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively impacts brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.
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BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a pivotal treatment for high-risk acute lymphocytic leukemia (ALL), although limited by suitable human leukocyte antigen (HLA)-matched sibling donors (MSD). This study evaluates the impact of donor selection on outcomes in post-HSCT Hispanic B-cell ALL patients. METHODOLOGY: This single-center retrospective study evaluates outcomes in 88 adult Hispanic B-cell ALL patients who underwent haploidentical, MSD, or MUD myeloablative HSCT between 2013 and 2023. RESULTS: Compared to Haploidentical transplants, MSD exhibited worse cumulative incidence of relapse (CIR) (HR = 3.39; P = 0.014) and disease-free survival (DFS) (HR = 2.44; P = 0.048) whereas MUD outcomes did not differ. This effect persisted even when controlling for pre-HSCT stage and Minimal residual disease (MRD) status. In addition, Ph-like was a significant predictor of worse DFS (HR = 3.60; P=0.014) and CIR (HR = 2.97; P=0.035) on multivariate analysis. Older donor age correlated with worse GVHD-free, relapse-free survival (GRFS) in haploidentical transplants (HR = 1.05; P=0.036). CONCLUSION: Our data highlights improved outcomes with younger, haploidentical donors among Hispanic B-cell ALL patients undergoing myeloablative HSCT. This underscores the importance of donor selection in optimizing outcomes for ALL patients.
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Selección de Donante , Trasplante de Células Madre Hematopoyéticas , Hispánicos o Latinos , Acondicionamiento Pretrasplante , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Femenino , Masculino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Acondicionamiento Pretrasplante/métodos , Adulto Joven , Adolescente , Donantes de Tejidos , Enfermedad Injerto contra Huésped/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Supervivencia sin Enfermedad , Resultado del Tratamiento , Hermanos , Tasa de SupervivenciaRESUMEN
Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m2 (1,600 mg) of cyclophosphamide ("pulse Cy"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized ("complete response") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting.
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INTRODUCTION: Detection of measurable residual disease (MRD) in adults with acute lymphoblastic leukemia (ALL) is a vital biomarker in risk prediction and treatment selection. Next-generation sequencing (NGS) offers greater sensitivity relative to multiparametric flow cytometry (MFC) and may be a better predictive tool for identifying ALL patients at risk of relapse. PATIENTS AND METHODS: This single-center retrospective study compares MRD detection by NGS versus MFC in 52 adult B- and T-ALL patients treated at our institution between 2018 and 2023. Pretreatment bone marrow samples were used for assay calibration, while post-treatment MRD assessment was completed up to 4.5 months after the first complete remission (CR1) using an MRD cutoff of 10-6 for distinguishing relapse risk. RESULTS: The 2-year cumulative incidence of relapse (CIR) among patients who were MRD positive using MFC and NGS was 39.5% and 46.2%, respectively. Unlike MFC, post-CR1 MRD positivity with NGS significantly predicted CIR (HR = 9.47, P = .028). In patients who were MRD negative by MFC, low levels of MRD detected by NGS distinguished patients at high risk of relapse (HR 10.3, P = .026, 2-year CIR 51.6%). CONCLUSION: Our data suggests that assessment of post-CR1 MRD using a highly sensitive NGS assay can identify ALL patients undergoing frontline therapy at increased risk of relapse and guide the use of adjuvant therapy.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Estudios Retrospectivos , Citometría de Flujo , Enfermedad Aguda , Recurrencia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Neoplasia Residual/diagnóstico , Neoplasia Residual/terapia , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
Background: Sweet Syndrome (SS) is a rare inflammatory skin condition characterized by the sudden appearance of tender, erythematous or violaceous papules, plaques, and nodules typically found on the face, neck, shoulder, upper extremities, and trunk. Often, SS is difficult to diagnose because of its various non-specific manifestations, including fever, arthralgia, myalgia and ocular involvement. In most cases described in literature, cutaneous and pulmonary symptoms of SS present in a concomitant manner. Several reported cases of pulmonary SS have shown that if left untreated, acute respiratory distress syndrome can ensue and progress to fatal respiratory failure. Case report: A 58-year-old female with acute myeloid leukemia (AML) secondary to chronic lymphocytic leukemia (CLL) presented with new nodular lesions, dyspnea, and fevers. Chest X-ray revealed pulmonary infiltrates. The patient developed new facial lesions and worsening hypoxic respiratory failure. Further infectious workup was negative. She was found to have SS with pulmonary involvement and initiated on high-dose intravenous (IV) steroids with marked clinical improvement. Conclusions: Major and minor criteria for the diagnosis of lung-associated SS should be carefully evaluated, especially when a biopsy is unavailable. The following case report describes the clinical course and outcomes from treatment for this patient.
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Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used to treat patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017 and 2020 using either cyclophosphamide (4 g/m2) plus granulocyte colony-stimulating factor (G-CSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. Although total CD34+ yield was higher after chemomobilization compared with G-CSF +/- PXF (median, 13.6 × 106/kg versus 4.4 × 106/kg; P < .01), achievement of ≥2 × 106 CD34+ cells (95% versus 93.7%; P = .61) and rates of mobilization failure (5% versus 6.3%; P = .61) were similar. Fewer patients required PXF with chemomobilization (12.3% versus 49.5%; P < .01), and apheresis sessions were fewer (median, 1 [range, 1 to 4] versus 2 [range, 1 to 5]). The rate of complications, including neutropenic fever, emergency department visits, and hospitalizations, was higher after chemomobilization (30% versus 7.4%; P < .01). Previous use of ≤6 cycles of lenalidomide did not impair cell yield in either group. The median cost of mobilization was 17.4% lower in the G-CSF +/- PXF group (P = .01). Between group differences in time to engraftment were not clinically significant. Given similar rates of successful mobilization, similar engraftment time, and less toxicity and lower costs compared with chemomobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure.
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Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Mieloma Múltiple , Antígenos CD34 , Bencilaminas , Ciclamas , Ciclofosfamida/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética , Compuestos Heterocíclicos/efectos adversos , Humanos , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Hepatic veno-occlusive disease (VOD/sinusoidal obstructive syndrome) represents a constellation of clinical findings including right upper quadrant pain, jaundice, hepatomegaly, and ascites. In the post-hematopoietic stem cell transplant (SCT) setting, the reported incidence has been 10-15%, with severe VOD historically resulting in high mortality rates. Novel agents including calicheamicin conjugated with CD33 (gemtuzumab ozogamicin; GO) and CD22 (inotuzumab ozogamicin; InO) are increasingly used for the treatment of acute myeloid leukemia and acute lymphoblastic leukemia, respectively. Both GO and InO are highly active, but also have unique hepatotoxicity profiles, including a higher risk of VOD in recipients of SCT. Introduction of GO and InO into pre-SCT leukemia management adds additional complexity to SCT patient selection and toxicity monitoring. In this article, we describe and review the risks and management associated with VOD in SCT recipients exposed to GO and InO.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Gemtuzumab , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/inducido químicamente , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Humanos , Inotuzumab Ozogamicina , Trasplante de Células Madre/efectos adversosRESUMEN
Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology. Overexpression of cyclin D1 and chromosome t(11,14) translocation are the known molecular biomarkers of this disease. Mantle cell international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation are emerging as the prognostic biomarkers. Epigenetic profile variance and SOX11 gene expression profile correlate with treatment response. Over the years, the treatment strategy has been gradually evolving from combination chemotherapy to combination of targeted therapy, epigenetic modulation therapy, and immunotherapy. In a surprisingly short period of time, FDA specifically approved 4 drugs for treating mantle cell lymphoma: lenalidomide, an immunomodulatory agent; Bortezomib, a proteasome inhibitor; and Ibrutinib and acalabrutinib, both Bruton kinase inhibitors. Epigenetic agents (e.g. Cladribine and Vorinostat) and mTOR inhibitors (e.g. Temsirolimus and Everolimus) have been showing promising results in several clinical trials. However, treating aggressive variants of this disease that appear to be refractory/relapse to multiple lines of treatment, even after allogeneic stem cell transplant, is still a serious challenge. Developing a personalized, precise therapeutic strategy combining targeted therapy, immunotherapy, epigenetic modulating therapy, and cellular therapy is the direction of finding a curative therapy for this subgroup of patients.
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Red cell aplasia has been rarely described in association with multiple myeloma. We present a case of a 79-year-old female, who was initially diagnosed with iron deficiency anemia, which did not improve with iron supplementation and required blood transfusions. Bone marrow biopsy showed red cell aplasia associated with kappa light chain multiple myeloma with 14.8% plasma cells. Further tests showed 0.35 g/dL M protein, and kappa/lambda ratio was 131.84. Cytogenetic showed deletion 13q, deletion 17p, loss of 1p and gain of chromosome 5. Multiple myeloma directed treatment with bortezomib and dexamethasone was initiated. Patient had clinical resolution of anemia and did not require further blood transfusions. This is an intriguing case of red cell aplasia associated with poor risk multiple myeloma (del 17p), which showed clinical improvement in anemia with bortezomib-based therapy. This case highlights the role of clonal plasma cells proliferation in the pathogenesis of red cell aplasia as myeloma directed treatment helped patient to become transfusion independent.
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The number of frail elderly individuals living in the United States is expected to increase. Frail patients tend to suffer from a number of chronic symptoms including pain, weakness and depression, and frailty is associated with dependence on others and increased mortality. Thus, palliative care is often appropriate for these individuals. This article describes frailty among the elderly, how frail patients might benefit from palliative care and several community-based programs that can improve the quality of life for home-bound frail elders.
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Enfermedad Crónica/terapia , Anciano Frágil/estadística & datos numéricos , Servicios de Salud para Ancianos/tendencias , Personas Imposibilitadas/estadística & datos numéricos , Cuidados Paliativos/tendencias , Dinámica Poblacional , Calidad de Vida , Anciano , Anciano de 80 o más Años , Estudios Transversales , Evaluación de la Discapacidad , Predicción , Necesidades y Demandas de Servicios de Salud/tendencias , Humanos , MinnesotaRESUMEN
OBJECTIVES: To presents socio-demographic characteristics and health seeking behaviour of elderly and to determine frequency of Diabetes Mellitus and Hypertension in elderly population of a poor peri-urban community in Karachi, Pakistan. METHODS: A cross-sectional study was conducted, targeting population aged 65 or above. A total of 438 respondents were interviewed after taking informed consent, between November 2005 and December 2005. Frequencies and Chi square values were calculated for different variables using SPSS 13.0. RESULTS: Total population surveyed comprised of 438 elderly, 158 (36%) women and 280 (63.9%) men. Mean age for the population was 71.44 +/- 7.74. A total of 238 (54.3%) elderly were found to be economically active. More than half (n = 269, 61.4%) of the elderly were found to be illiterate. Only 72 (16.4%) of the elderly population were Diabetic and 132 (30.1%) were Hypertensive. Common symptoms that prompted elderly of Azam Basti to seek health care were fever (61.2%), generalized body aches (43.4%) and cough (40.4%). Over half of the (n = 269, 61.4%) responders reported factors which deterred them from seeking health care, out of which 62% reported financial constraint as the commonest factor. Deterrence from seeking health care was associated with illiteracy (p = 0.001) and living alone (p = 0.06). CONCLUSION: The elderly population of this peri-urban community has financial constraints in seeking health care. Hypertension was found to be more prevalent among women as compared to men, ratio being 1:2. Less number of people knew they were diabetics; this might be attributed to ignorance and non-availability of investigations and screening.
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Actitud Frente a la Salud , Accesibilidad a los Servicios de Salud , Estado de Salud , Aceptación de la Atención de Salud/estadística & datos numéricos , Anciano , Estudios Transversales , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Pakistán/epidemiología , Pobreza , Factores Sexuales , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
A 62-year-old male patient presented with right flank pain and right renal mass on CT scan. Patient left against medical advice and had nephrectomy done elsewhere. Histopathology revealed a diffuse large cell B-cell lymphoma. Patient presented again, with disseminated disease and was started on chemotherapy. Although a rare disorder, missing primary renal lymphoma as one of the causes of renal mass can lead to disseminated disease and unnecessary nephrectomy, in spite of chemotherapy being standard management.
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Neoplasias Renales/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/cirugía , Masculino , Persona de Mediana Edad , Nefrectomía , Prednisolona , VincristinaRESUMEN
In this study, the response of Imitanib Mesylate in patients with Gastro-intestinal stromal cell tumour (GIST) was assessed. GIST results from a mutation in one of the receptor protein tyrosine kinases. Imitanib Mesylate, a tyrosine kinase inhibitor, has emerged as a promising new treatment for GISTs. Total 16 cases were reviewed. Diagnosis was based on biopsy and immunohistochemistry. Response assessment was done using CT scans, at a median duration of 4 months. The median age of the patients was 52 years, Majority were male (n=14). Most common presenting complaint was abdominal pain (n=7). Commonest primary site was stomach (n=7), Liver was the most common organ involved in metastasis (n=8). All patients received Imitanib 400 mg orally, once a day. No mortality was reported during median follow up time of 28 months on Imitanib. There was also either radiological remission (n=5) or response (n=5), in about half of the patients without any serious side effects.