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Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT's efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 106 CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections for elderly patients and efficient management of excess PBSCs to optimize resource utilization.
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Venetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real-world data published on HMAs plus VEN have been either single-center studies or using community-based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real-world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85-13.5), with OS significantly worse among patients with TP53-mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30-day and 60-day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE-A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Anciano , Humanos , Estudios Retrospectivos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Sulfonamidas/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Sudden blast crisis is an uncommon phenomenon in chronic myeloid leukemia (CML) patients who are being treated with tyrosine kinase inhibitors (TKIs). Despite well-defined guidelines to treat and monitor the disease, it is difficult to predict the occurrence of a sudden blast crisis. Research directed towards improving guidelines in choosing the appropriate TKIs and better monitoring protocols could help prevent such unfortunate outcomes. We present a case of a 46-year-old man diagnosed with CML who responded well to imatinib as evidenced by a downtrend in quantitative BCR-ABL mutation to less than 1. He quickly transformed into a blast crisis phase after five months of therapy with imatinib regardless of achieving an excellent initial optimal response. In conclusion, it is possible to transform into a blast phase despite achieving an initial optimal response. Therefore, attention should be focused on the selection of proper tyrosine kinase inhibitors and careful monitoring to allow the early detection of sudden blast crisis.
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Multiple myeloma (MM) is an incurable clonal B-cell malignancy that usually presents with neoplastic monoclonal plasma cells in either bone or soft tissues. Central nervous system involvement of the myeloma (CNS-MM), such as dural myeloma or intraparenchymal infiltration, or diffuse leptomeningeal involvement, is uncommon. Dural involvement of myeloma without parenchymal or leptomeningeal disease is even rarer, with only seven cases reported previously. We present a case of epidural myeloma in a 50-year-old man with known kappa light chain MM, presenting with multiple episodes of subdural hemorrhage and progressive neurological deficits. He initially presented with severe back pain, hypercalcemia, and acute kidney injury (AKI). Further evaluation showed lytic bone lesions and elevated kappa light chains, and bone marrow biopsy showed 32% of clonal plasma cells. He was initially treated with bortezomib, lenalidomide, and dexamethasone combination, followed by pomalidomide and daratumumab. Eventually, he developed two episodes of subdural hemorrhage and left-sided seventh cranial nerve palsy, which was treated conservatively and monitored by computed tomography (CT) of the head. However, he gradually developed multiple cranial nerve palsies, weakness, and urinary incontinence. Cerebrospinal fluid (CSF) analysis showed elevated protein without any aberrant immunophenotype. Magnetic resonance imaging (MRI) of the brain showed diffuse smooth dural enhancement with extensive calvarial and skull base marrow replacement; MRI of the spine showed diffuse epidural enhancement in thoracic and lumbar regions, findings consistent with epidural myeloma. The patient received three doses of cranial irradiation but, unfortunately, could not tolerate further treatment and opted for hospice care. Intracranial hemorrhage is common in MM patients, and it is important to consider CNS involvement in patients presenting with recurrent subdural hemorrhage and to perform imaging (preferably MRI) earlier in the disease course. Due to its rarity, the treatment of CNS-MM is very heterogeneous. Thus, case reporting is important to accumulate data on this rare presentation.
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PURPOSE: Acute promyelocytic leukemia (APL) is a curable leukemia with > 90% survival in clinical trials. Population-based studies from Sweden and US SEER data have shown long-term survival rates of 62% and 65.7%, with the lower rate being from a higher percentage of early deaths. METHODS: In this prospective, multicenter trial, we developed a simplified algorithm that focused on prevention and early treatment of the three main causes of death: bleeding, differentiation syndrome, and infection. All patients with a diagnosis of APL were included. The initial 6 months were spent educating oncologists about early deaths in APL. At the time of suspicion of an APL, an expert was contacted. The algorithm was made available followed by discussion of the treatment plan. Communication between expert and treating physician was frequent in the first 2 weeks, during which time most deaths take place. RESULTS: Between September 2013 and April 2016, 120 patients enrolled in the study from 32 hospitals. The median age was 52.5 years, with 39% > 60 years and 25% with an age-adjusted Charlson comorbidity index > 4. Sixty-three percent of patients were managed at community centers. Two patients did not meet the criteria for analysis, and of 118 evaluable patients, 10 died, with an early mortality rate of 8.5%. With a median follow-up of 27.3 months, the overall survival was 84.5%. CONCLUSION: Induction mortality can be decreased and population-wide survival improved in APL with the use of standardized treatment guidelines. Support from experts who have more experience with induction therapy is crucial and helps to improve the outcomes.
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Leucemia Promielocítica Aguda , Hemorragia , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Persona de Mediana Edad , Estudios Prospectivos , Suecia , UniversidadesRESUMEN
Treatment of acute leukemia has been delivered predominantly in academic and larger leukemia treatment centers with the infrastructure and staff needed to manage patients receiving complex therapeutic regimens and supportive care. However, in recent years, several oral agents and less-myelosuppressive regimens were approved, making it possible for these patients to receive therapy in smaller community hospitals and oncology office practices. In this review, we discuss the optimum community setting, type of patient who can be treated, agents that can be applied, and an appropriate clinical circumstance in which a referral to a tertiary center should be made.
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Centros Comunitarios de Salud Mental , Leucemia/terapia , Enfermedad Aguda , Humanos , Derivación y ConsultaRESUMEN
We sought to evaluate the outcomes of chronic phase (CP) chronic myeloid leukemia (CML) in an era where five tyrosine kinase inhibitors (TKIs) are commercially available for the treatment of CML. Records of patients diagnosed with CP CML, treated with TKIs and referred to our center were reviewed. Between January 2005 and April 2016, 206 patients were followed for a median of 48.8 (1.4-190.1) months. A total of 76 (37%) patients received one TKI, 73 (35%) received two TKIs and 57 (28%) were exposed to >3 TKIs (3 TKIs, n = 33; 4 TKIs, n = 17; 5 TKIs, n = 7). Nineteen (9.2%) patients progressed to advanced phases of CML (accelerated phase, n = 6; myeloid blastic phase, n = 4; lymphoid blastic phase, n = 9). One third (n = 69) achieved complete molecular response (CMR) at first-line treatment. An additional 55 patients achieved CMR after second-line treatment. Twenty-five patients (12.1%) attempted TKI discontinuation and 14 (6.8%) stopped TKIs for a median of 6.3 months (range 1-53.4). The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs). The best OS was observed in patients tolerating and responding to first line TKI, but multiple TKIs led patients to gain treatment-free remission.
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Intensive treatment for newly diagnosed acute myelogenous leukemia (ND-AML) patients are reserved for "fit" patients. While guidelines recommend evaluation of age, performance status and comorbidities, there is no consensus on the definition of "fitness" or optimal therapy for elderly AML patients. This retrospective study evaluated characteristics and survival outcomes of 274 patients (age ≥60 years) with ND-AML treated with 7 + 3 (cytarabine + an anthracycline) vs. hypomethylating agents (HMAs). Most patients received 7 + 3 (60.2%) vs. HMAs (39.8%) in first-line therapy (1 L T); more HMA patients were ≥75 years old and had more comorbidities. Median progression-free survival (PFS) following 1 L T was longer for patients who received 7 + 3 vs. HMAs (6.7 months [95% confidence interval (CI)]: 4.9, 11.1) vs. 4.1 months (95% CI: 2.8, 4.9, respectively). Median overall survival (OS) following 1 L T was also longer for patients who received 7 + 3 vs. HMAs (14.7 months [95% CI: 11.0, not estimated] vs. 4.3 months [95% CI: 3.2, 5.8], respectively). An age-adjusted Charlson Comorbidity Index score of ≥4 vs. < 4 negatively affected PFS and OS irrespective of treatment. Overall, choosing an HMA over 7 + 3 in elderly patients with ND-AML may be influenced by age and comorbidities; patients receiving 7 + 3 had longer survival than those on an HMA.
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Antineoplásicos/administración & dosificación , Quimioterapia de Inducción/métodos , Leucemia Mieloide Aguda/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND Essential thrombocythemia (ET) is one of the BCR-ABL gene fusion negative chronic myeloproliferative disorders (MPDs), which also include polycythemia vera (PV), and myelofibrosis. Few clinical cases have reported the progression of ET to chronic myelogenous leukemia (CML) with the expression of the BCR-ABL gene. This report describes such a case and includes a review of other reported cases of CML co-occurring with BCR-ABL-negative chronic MPDs. CASE REPORT A 49-year-old woman was diagnosed with ET in 2007. Cytogenetic testing was negative for expression of the JAK2 or BCR-ABL1 genes. Eight years later, in January 2015, she presented with excessive fatigue, poor appetite, unintentional weight loss, a white blood cell (WBC) count of 24,700 per mL, hemoglobin of 9.9 g/dl, and a platelet count of 557,000 per mL, with blasts and basophils in the blood film. Cytogenetic analysis with fluorescent in situ hybridization (FISH) confirmed a 9: 22 chromosomal translocation (Philadelphia chromosome), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression of the BCR-ABL gene, confirming a diagnosis of CML. In February 2015, first-line therapy commenced with nilotinib, which was changed to imatinib after three months. During the following nine months, qRT-PCR confirmed a trend to deep molecular remission (MR5). However, she developed early myelofibrosis, and myelosuppressive therapy was resumed. CONCLUSIONS This rare case highlights the importance of cytogenetic testing in cases of CMPD that transform to CML, not only to confirm the diagnosis but to plan treatment, as Philadelphia chromosome-positive and -negative cases differ in their management.
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Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Trombocitemia Esencial/etiología , Femenino , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Translocación GenéticaRESUMEN
To describe patient characteristics and treatment patterns among elderly patients (≥66 years) newly diagnosed with acute lymphoblastic leukemia (ALL), we analyzed 100% Medicare ALL data from 2007 to 2015. Only 764 out of 1428 (53.5%) elderly patients received treatment within 90 d of diagnosis with ≥30-d follow-up; 32.4% received chemotherapy without tyrosine kinase inhibitors (TKIs), 8.8% received both chemotherapy and TKIs, 9.8% received steroids only and 2.6% received TKIs only. Among 717 patients receiving chemotherapy any time during follow-up, 65.8% received only one course of treatment. Patients treated with chemotherapy or TKIs compared to untreated patients were younger (<75 years: 51.5 vs. 21.7%) and had a lower comorbidity burden (Charlson Comorbidity index ≤ 2: 90.9 vs. 71.4%). Overall, 67.5% of patients died within 3 years of diagnosis. Our findings demonstrate that many elderly ALL patients are not treated in the real-world setting and highlight the need for tolerable therapies for these patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Reclamos Administrativos en el Cuidado de la Salud/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Centers for Medicare and Medicaid Services, U.S./estadística & datos numéricos , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Medicare/estadística & datos numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
Bosutinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI), has been available for several years as a treatment for chronic-, accelerated-, and blast-phase chronic myeloid leukemia (CML), for patients with resistance or intolerance to prior therapy. In 2017, the BFORE trial demonstrated efficacy of bosutinib as first-line treatment in adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). The most common adverse events (AEs) of any grade in bosutinib-treated patients in BFORE were diarrhea, nausea, thrombocytopenia, increased alanine aminotransferase, and increased aspartate aminotransferase, consistent with the most commonly reported AEs in earlier studies. To balance the efficacy and tolerability of treatment to optimize patient adherence with medications, treating physicians commonly use various strategies such as initiating treatment at a lower dose, dose reduction, or dose interruption, depending on the type and severity of the AEs and the clinical setting. In light of the recent data from first-line treatment, an expert panel of hematologists reviewed management strategies for the use of bosutinib in treatment of CP-CML and made the recommendations reported here. Although the panel focused on first-line treatment, the principles can be for the most part extended to bosutinib use in later lines of treatment. Recommendations include advice regarding prophylaxis and management for diarrhea. The panel also considered optimum timing for referral to a specialist for specific AEs. Across the commonly occurring AEs, the panel highlighted the importance of education and communication with patients about anticipated AEs.
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Compuestos de Anilina/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Nitrilos/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Quinolinas/efectos adversos , Compuestos de Anilina/farmacología , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Nitrilos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Quinolinas/farmacologíaRESUMEN
BACKGROUND Tamiflu (oseltamivir phosphate) serves as prophylaxis and treatment of upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) caused by viruses of the Orthomyxovirus family. Here, we present a patient with URTI and negative rapid influenza diagnostic testing (RIDT), who developed rhabdomyolysis after being started on oseltamivir. CASE REPORT Our report describes a rare case of rhabdomyolysis after oseltamivir administration in a 53-year-old man with suspected influenza. We discuss the differential diagnosis for rhabdomyolysis to rule out other causes and review the literature on influenza-induced rhabdomyolysis. CONCLUSIONS Considering the serious consequences of rhabdomyolysis, care needs to be taken in routine prescription and use of oseltamivir. Although this is a rare adverse effect, our case highlights the need to be vigilant for uncommon adverse events with commonly used drugs.
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Antivirales/efectos adversos , Gripe Humana/tratamiento farmacológico , Oseltamivir/efectos adversos , Rabdomiólisis/inducido químicamente , Antivirales/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Oseltamivir/uso terapéuticoRESUMEN
Inhibition of the Janus-associated kinases (JAK) with ruxolitinib (RUX) reduces graft-versus-host disease (GVHD) in preclinical and clinical models. In total 19 allograft recipients with moderate/severe steroid-dependent chronic GVHD received RUX as ≥2nd line salvage. RUX was well tolerated, and led to complete/partial resolution of oral (92/7%), cutaneous (82/0%), hepatic (71/28%), gastro-intestinal (75/17%), musculoskeletal (33/67%), pulmonary (0/80%), scleroderma (0/75%), vaginal (0/75%), and ocular (0/100%) chronic GVHD. Overall 18 achieved partial response and 1 complete response according to NIH Consensus Criteria. Responses occurred early and were sustained which enabled discontinuation (68%) or reduction of steroids to physiologic doses (21%). We conclude that RUX is an effective steroid-sparing agent in chronic GVHD.
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Enfermedad Injerto contra Huésped/tratamiento farmacológico , Quinasas Janus/uso terapéutico , Pirazoles/uso terapéutico , Adulto , Anciano , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/patología , Humanos , Quinasas Janus/farmacología , Masculino , Persona de Mediana Edad , Nitrilos , Pirazoles/farmacología , PirimidinasRESUMEN
The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term safety of these agents is a growing concern. We identified 20 patients with CP-CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. Second-generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1). One other patient initiated therapy with ponatinib on trial. Response was assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) for BCR-ABL1 levels every 3 months and in patients with qRT-PCR values less than 10% at 3 months, IM was started at 400 mg/d. IM was well tolerated except in 2 patients who required dose-reduction and discontinuation due to grade 2 skin rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR-ABL1 qRT-PCR levels trended down as expected. At 12 months 16 (84.2%) of 19 evaluable patients showed a 3 log (major molecular remission) or better reduction in their PCR levels. In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G-TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.
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Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Dasatinib/uso terapéutico , Esquema de Medicación , Femenino , Proteínas de Fusión bcr-abl/genética , Regulación Leucémica de la Expresión Génica , Humanos , Mesilato de Imatinib/uso terapéutico , Imidazoles/uso terapéutico , Leucemia Mieloide de Fase Crónica/genética , Masculino , Persona de Mediana Edad , Piridazinas/uso terapéutico , Pirimidinas/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: To the authors' knowledge, the optimal frequency of monitoring after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic myeloid leukemia (CML) has not been established. Data regarding the discontinuation of second-generation TKIs used in first-line treatment or after the failure of first-line treatment with TKIs are limited. Herein, the authors report real-world experience with "reduced frequency" molecular monitoring in patients with CML in all phases who discontinued treatment with imatinib, dasatinib, or bosutinib. METHODS: The records of patients who discontinued TKIs were reviewed. Patients who discontinued TKIs were monitored prospectively on an intended schedule of monthly blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 for 3 months, quarterly for 12 months, and every 6 months thereafter until loss of major molecular response (MMR). After loss of MMR, the TKI that previously was discontinued was reinitiated. RESULTS: Between January 2010 and September 2015, a total of 24 patients in chronic (21 patients), accelerated (2 patients), and lymphoid blast (1 patient) phase discontinued imatinib (16 patients), dasatinib (5 patients), or bosutinib (3 patients) used in the front-line treatment or beyond. Blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 was performed 1.3 ± 0.7 times within the first 3 months (24 patients) and 2.7 ± 1.4 times in the following 12 months (18 patients). With a median follow-up of 36.5 months (range, 3.2-67.4 months), the probabilities of treatment-free remission at 1 year and 2 years were 65.7% (95% confidence interval, 55.8%-75.6%) and 59.7% (95% confidence interval, 49.1%-70.3%), respectively. Loss of MMR was observed in 9 patients at a median of 2.8 months (range, 1.8-14.2 months) after discontinuation of TKIs. CONCLUSIONS: With the limitations of a small sample size, the results of the current study demonstrate that less frequent monitoring of BCR-ABL1 does not appear to affect outcomes, and that discontinuation of TKIs used as first-line treatment or beyond after resistance or intolerance to first-line treatment appears feasible. Cancer 2017;123:2482-88. © 2017 American Cancer Society.
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Deprescripciones , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Recurrencia Local de Neoplasia/sangre , Inhibidores de Proteínas Quinasas/uso terapéutico , Espera Vigilante/métodos , Adulto , Anciano , Anciano de 80 o más Años , Compuestos de Anilina/uso terapéutico , Dasatinib/uso terapéutico , Femenino , Humanos , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Nitrilos/uso terapéutico , Quinolinas/uso terapéutico , Inducción de Remisión , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Posaconazole is a commonly used medication for antifungal prophylaxis in patients with high-risk acute leukemia, such as acute myeloid leukemia. Despite clinical data that show that posaconazole is superior to other antifungal prophylaxis medications, posaconazole is known to have many side effects and drug-drug interactions. We present a patient who developed rhabdomyolysis after being started on posaconazole for prophylaxis in the setting of relapsed acute myeloid leukemia.
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INTRODUCTION: The effect of post-transplant maintenance tyrosine kinase inhibitors (TKIs) on the outcomes of allogeneic hematopoietic stem cell transplantation in high-risk Philadelphia chromosome-positive (Ph(+)) leukemia remains unknown. PATIENTS AND METHODS: A retrospective analysis that included allograft recipients with accelerated phase and blast phase chronic myeloid leukemia or Ph(+) acute lymphoblastic leukemia who had received post-transplant maintenance TKI therapy from 2004 to 2014. RESULTS: A total of 26 patients, 9 with accelerated phase/blast phase CML and 17 with Ph(+) acute lymphoblastic leukemia, received maintenance post-transplant therapy with imatinib, dasatinib, nilotinib, or ponatinib. The TKI was selected according to the pretransplantation TKI response, anticipated toxicities, and ABL1 domain mutations, when present. Newer generation TKIs were initiated at a ≥ 50% dose reduction from the standard pretransplantation dosing to limit the toxicities and avoid therapy interruptions. TKIs were started a median of 100 days (range, 28-238 days) after transplantation and were administered for a median of 16 months (range, 8 days to 105 months). Eight patients discontinued therapy because of adverse events. With a median follow-up of 3.6 years (range, 4 months to 8.7 years), the 5-year relapse-free survival rate was 61%. All 3 patients who developed a relapse underwent successful salvage treatment and remained disease-free. The 5-year overall survival rate was 78%. CONCLUSION: Maintenance TKI therapy after transplantation is feasible and might reduce the incidence of relapses and improve outcomes after allogeneic hematopoietic stem cell transplantation for patients with high-risk Ph(+) leukemia.
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Antineoplásicos/uso terapéutico , Leucemia/genética , Leucemia/terapia , Cromosoma Filadelfia , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Terapia Combinada , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Posoperatorios , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios Retrospectivos , Análisis de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Acute myeloid leukemia (AML) is a myeloid disorder with several established treatment regimens depending on patient and leukemic factors. Cisplatin is known to have strong leukemogenic potential and is rarely used even as salvage therapy in relapsed or refractory AML. We present a patient simultaneously diagnosed with AML and squamous cell carcinoma of the larynx, who was found to be in complete remission from AML following treatment with cisplatin based chemoradiotherapy for his laryngeal cancer.