Acute Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The Good, the Bad, and the Ugly of Isolated Extramedullary Relapse in a Latin American Population.

Hematopoietic stem cell transplantation (HSCT) is an effective therapy for acute leukemia (AL). Relapse represents the main cause of mortality. Isolated extramedullary relapse (iEMR) is atypical and has been related to better outcomes. Here we describe the clinical characteristics and outcomes of AL relapse after HSCT in our study population and analyze the impacts of different types of relapse on survival outcomes. This retrospective, multicenter study included 124 patients age ≥15 years with AL who underwent HSCT between 2004 and 2019. At diagnosis, 66.1% of the patients had lymphocytic AL, 19.7% presented with high-risk features, and 18.5% had extramedullary disease (EMD). At HSCT, 83.1% of the patients were in complete remission (CR), and 44.8% had negative measurable residual disease (MRD). The vast majority of donors were related (96%), including 48.4% HLA-matched and 47.6% haploidentical. Myeloablative conditioning was provided to 80.6% of patients. The median overall survival (OS) was 15 months (95% confidence interval [CI] 9.9 to 20.1 months). Factors associated with improved OS were adolescent and young adult (AYA) patient (P = .035), first or second CR (P = .026), and chronic graft-versus-host disease (GVHD) (P < .001). Acute GVHD grade III-IV (P = .009) was associated with increased mortality. The median relapse-free survival was 13 months (95% CI, 7.17 to 18.8 months); early disease status (P = .017) and chronic GVHD (P < .001) had protective roles. Sixty-eight patients (55%) relapsed after HSCT, with a median time to relapse of 6 months (95% CI, 3.6 to 8.4 months). iEMR was reported in 16 patients (23.5%). The most commonly involved extramedullary sites were the central nervous system and skin. Compared to patients with bone marrow relapse, all patients with iEMR had a diagnosis of acute lymphoid leukemia (P = .008), and 93.8% belonged to the AYA group; regarding pre-HSCT characteristics, iEMR patients had higher rates of negative MRD (P = .06) and a history of EMD (P = .009). Seventy-seven percent of relapsed patients received additional treatment with curative intent. The median OS after relapse (OSr) was 4 months (95% CI, 2.6 to 5.4 months). Factors related to increased OSr included lymphoid phenotype (P = .03), iEMR (P = .0042), late relapse (≥6 months) (P = .014), receipt of systemic therapy including second HSCT (P < .001), and response to therapy (P < .001). Rates of relapse and iEMR were higher than those previously reported in other studies. Advanced disease, reduced-intensity conditioning, and a diminished graft-versus-leukemia effect were factors influencing these findings. At relapse, presenting with iEMR after 6 months and receiving intensive therapy with adequate response were associated with better outcomes. Our results strongly suggest that a personalized approach to treating patients with HSCT is needed to counterbalance specific adverse factors and can positively impact clinical outcomes.

Hematopoietic stem cell transplantation activity in Mexico during the COVID19 pandemic: on the way to recovery.

OBJECTIVE: To analyze the number of HSCTs performed in 2019 vs. 2020 and report the status of transplant centers (TCs) during and a year after the COVID-19 pandemic. METHODS: We performed a comprehensive cross-sectional nationwide study including active TCs interrogating HSCT activity from 2019 through September 2021. An electronic survey was sent to TCs and consisted of items regarding the number and characteristics of procedures performed and were compared yearly. Changes to their institutions' transplant policies and practices during the COVID19 pandemic were also documented. Fifty centers were invited to participate, 33 responded. RESULTS: Most TCs were part of the public health system (63.7%). Almost half are in the country's capital, Mexico City (45.5%). Most centers performed <10 procedures per year. The number of HSCTs decreased from 835 in 2019-505 in 2020 (p < .001), representing a 40% reduction in transplant activity. The monthly transplant rate in 2021 increased to 58.3, compared to 42 in 2020 and close to 69.5 in 2019 (p < .001). All types of HSCTs decreased excluding haploidentical transplants. All institutions treated patients with COVID19, and over two-thirds experienced some form of hospital reconversion. Transplant activity stopped completely in 23 TCs (70%) during the pandemic with a median closure duration of 9.9 months (range, 1-21). In 2021, 9.1% of TCs remained closed, all of them in the public setting. CONCLUSION(S): The limited transplant activity in Mexico decreased significantly during the pandemic but is recovering and nearly in pre-pandemic levels.

Impact of Socioeconomic Characteristics and Comorbidities on Therapy Initiation and Outcomes of Newly Diagnosed Multiple Myeloma: Real-World Data From a Resource-Constrained Setting.

BACKGROUND: Outcomes of newly diagnosed multiple myeloma (NDMM) in developing regions have not paralleled those in developed settings. Economic disadvantage, comorbidities, and aggressive disease behavior play competing roles on defining outcomes. Our aim was to analyze the impact of socioeconomic characteristics and comorbidities on therapy initiation, drug selection, and survival outcomes of NDMM in a resource-constrained setting. PATIENTS AND METHODS: This retrospective single-center cohort included ≥ 18-year-old NDMM patients from January 2006 to December 2018. RESULTS: A total of 245 patients were included with a median age of 62 years, Eastern Cooperative Oncology Group performance status ≤ 2 in 70.2%, International Staging System score ≥ 2 in 89.4%, and high-risk disease in 31.6%. Comorbidities were reported in 69.4%, and Charlson comorbidity index (CCI) was ≥ 2 in 64.1%. A total of 87.4% (n = 214) received thalidomide-, alkylating-, and bortezomib-based induction in 67.8%, 18.2%, and 13.1%. Patient-related factors including performance status, comorbidities, and CCI, but not myeloma-related factors, were associated with a decreased likelihood of initiating induction therapy. On multivariate analysis, CCI ≥ 2 remained statistically significant (odds ratio, 5.81; P = .005). Overall survival was 44 months. Although both patient- and myeloma-related factors were associated with a decreased overall survival, only International Staging System score > 2 (hazard ratio, 3.53; P = .004) and induction without bortezomib-based regimens (hazard ratio, 4.45; P < .001) were statistically significant on multivariate analysis. CONCLUSION: Myeloma- and treatment-related factors are the main determinants of survival in NDMM induction-eligible patients. Patient-related factors play a pivotal role determining access to therapy and survival outcomes. Comorbidity index and performance status were determinant on defining therapy initiation in this real-world population, which emphasizes the need to improve health baseline conditions in resource-constrained settings.

Access to Palliative Care Services and Clinical Outcomes of Patients With Solid Malignancy-Associated Myelophthisis in a Resource-Limited Setting.

BACKGROUND: Myelophthisis (MPT) has been associated with a dreadful prognosis. Patients' access to palliative care (PC) and factors influencing its clinical outcomes are poorly described. Our aim was to analyze the impact of patient- and disease-specific characteristics on survival of patients with MPT and describe their use of PC in a resource-limited setting. METHODS: Retrospective study including patients with solid tumor MPT, diagnosed between 1996 and 2018. RESULTS: Seventy patients (median 58 years) were included. 58% were synchronously diagnosed with MPT at time of primary tumor diagnosis. Most common oncologic diagnoses were prostate (25.7%), gastrointestinal (20%), and breast (18.6%) neoplasms. Median overall survival (OS) was 1.9 months. Primaries other than prostate, breast, and lung (HR 1.37, 95% CI 1.15 - 1.8; p = 0.02) and transfusion requirements (HR 2.8, 95% CI 1.01 - 7.9; p = 0.04) were independently associated with decreased OS. Administration of multiple systemic therapeutic interventions (HR 0.15, 95% CI 0.06 - 0.39; p = 0.01) was the sole factor improving OS. Assessment by PC was pursued in 51.4% of patients. The median number of consults per patient was two, with no difference in assessment rate or consult number across different primaries (P = 0.96). Four cases of palliative sedation were reported, all performed by the primary care team. CONCLUSION: MPT is highly heterogeneous and risk stratification to optimize the use of therapeutic interventions in unison with palliative interventions is needed to maximize efforts toward improving patient quality of life. There is an alarming need of PC services in the multidisciplinary management of patients within developing regions.

Mycobacterium genavense invading the bone marrow in a HIV-positive patient.

Nontuberculous mycobacteria infrequently cause disseminated infections in immunocompetent hosts. However, they are increasingly being recognized in immunocompromised patients. We present the case of a 40-year-old HIV-positive male presenting with lymphadenopathies and pancytopenia in whom disseminated infection, with bone marrow involvement by Mycobacterium genavense (M. genavense) was diagnosed.

Fluorescent In Situ Hybridization Monitoring and Effect of Detected Early Responses in the Outcome of Patients With Chronic Phase Chronic Myeloid Leukemia: A Report From a Latin American Country.

INTRODUCTION: The cytogenetic hallmark of chronic myeloid leukemia (CML) is the Philadelphia chromosome. Monitoring the response in patients receiving therapy is a standard of care. The present study was conducted to assess the monitoring adherence and reliableness of fluorescent in situ hybridization (FISH) as a monitoring tool and the effect of a complete cytogenetic response (CCyR) assessed by FISH on the prognosis of patients in a chronic phase (CP)-CML cohort. MATERIALS AND METHODS: We retrospectively analyzed the data from 63 newly diagnosed CP-CML patients treated with imatinib mesylate at a dose of 400 mg/day as frontline therapy. The clinical data and cytogenetic test results at diagnosis and during monitoring were collected. The cytogenetic monitoring adherence assessment rates were measured. A correlation between chromosome banding analysis (CBA) and FISH was performed. The CCyR assessed by FISH was defined as < 1% BCR-ABL1(+) nuclei. The Kaplan-Meier method was used for overall survival analysis and time-to-event estimates. RESULTS: The cytogenetic monitoring assessment adherence was 50.8% at 3 months, 93.5% at 6 months, 96.7% at 12 months, and 88.6% at 18 months. The Pearson correlation coefficient showed a significantly positive association (r = 0.84; P < .001) between CBA and FISH. The median follow-up duration after imatinib mesylate initiation was 60 months. A CCyR was achieved in 90.4% of patients within the first 18 months of therapy. At 3 months, 31 patients underwent a FISH evaluation, and 13 (41.9%) had achieved a CCyR. The patients who did not achieve a CCyR at 3 months had a significantly inferior probability of 5-year failure-free survival (38% vs. 94%; P = .001) and progression-free survival (80% vs. 100%; P = .043) compared with those with a CCyR. CONCLUSION: We found improved monitoring adherence compared with the previous reports of Latin American populations. In countries with a high incidence of failure for CBA and a lack of real-time polymerase chain reaction standardization, FISH is a sensitive monitoring tool. In our cohort, patients not achieving an early CCyR, as tested by FISH, were a poor prognosis subgroup with worse rates of failure-free survival and progression-free survival.

Autoantibodies in prediction of the development of rheumatoid arthritis among healthy relatives of patients with the disease.

OBJECTIVE: Although blood bank-based studies have shown that rheumatoid arthritis (RA)-related autoantibodies are present before the onset of RA, information on their positive predictive value (PPV) for development of RA in healthy individuals is scarce. This study was undertaken to assess the 5-year PPV of serum IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) for the development of RA among healthy relatives of patients with RA. METHODS: Healthy relatives of RA patients were invited to participate in a cohort study. At baseline, information on participants' medical history was obtained, and serum levels of IgM-RF and anti-CCP antibodies were determined (by nephelometry and second-generation anti-CCP enzyme-linked immunosorbent assay, respectively). The subjects were followed up every 4 months via a structured interview (Community Oriented Program for Control of Rheumatic Diseases [COPCORD] questionnaire). When the COPCORD questionnaire indicated possible arthritis, subjects underwent an in-office rheumatology assessment including joint count. The study end point was defined as fulfillment of the American College of Rheumatology criteria for RA. RESULTS: Eight hundred nineteen initially healthy relatives of 252 patients with RA were included (69% female, 41% offspring, mean ± SD age 35 ± 12 years). Eleven (1.3%) were positive for both anti-CCP-2 and RF, 12 (1.5%) only for anti-CCP-2, and 16 (2%) only for RF. RA developed in 17 (2.1%) of the relatives during the 5-year followup (3,313 person-years for the seronegative group and 60.8 person-years for the anti-CCP-2-positive group). The PPV was 64% when both anti-CCP-2 and RF were positive and 58% when only anti-CCP-2 was positive. Offspring of patients with RA had an independent 3-fold increased risk of developing RA. CONCLUSION: Results of the present study indicate that the magnitude of risk for developing RA in healthy relatives of patients with RA can be estimated using simple routine laboratory tests.

The number needed to offend: a cross-sectional study of potential offensiveness of rheumatic diagnostic labels.

This study aims to explore the different connotations and potential offensiveness of ten mechanistic labels in newly referred Mexican patients with rheumatic symptoms as well as in Mexican and Canadian rheumatologists. Patients with musculoskeletal complaints newly referred for a rheumatology assessment were interviewed consecutively before they saw the rheumatologist. Patients were asked to choose one of nine feelings provoked by ten different illness mechanism labels. Rheumatologists gave a medical diagnosis after seeing the patients. Mexican and Canadian rheumatologists were invited to answer a structured questionnaire about their feelings at the moment they identified each of the ten different provided scenarios. Patients' and rheumatologists' feelings were classified as "offended" or "nonoffended." The "offensive score" was used to calculate a "number needed to offend" (NNO). One hundred and fifty patients were included. Inherited, immunological, and inflammatory labels had the fewest negative connotations (NNOs 17, 12, and 14, respectively), and psychological, functional, idiopathic, and sleep disturbance labels had the most (NNO 2 and 3, respectively). Functional labels were almost four times more offensive than organic labels. Stratified by rheumatologist diagnosis, patients with functional disorders were more accepting of organic-based mechanistic labels. A higher potential to offend was observed when patients with functional somatic conditions were given functional mechanistic labels (NNOs 1 to 4). The survey was completed by 186 Mexican rheumatologists and 71 Canadian rheumatologists. Primarily functional disorders such as somatization and anxiety had a high potential to evoke offensive feelings (NNOs 3 to 7). No significant differences in the NNO were found between Mexican and Canadian rheumatologists. Getting or giving mechanistic/explanatory labels is emotional. Both patients and rheumatologists experienced offended feelings with functional or idiopathic labels.

Sustained clinical remission and rate of relapse after tocilizumab withdrawal in patients with rheumatoid arthritis.

OBJECTIVE: Data on when to stop use of biological agents in rheumatoid arthritis (RA) are scant. We assessed the length of remission and the rate of clinical relapse in patients with RA who had to discontinue treatment with tocilizumab (TCZ) because of the ending of longterm (5 yrs) open-label clinical trials. METHODS: All patients at 2 participating centers in Mexico were in remission, defined as Disease Activity Score 28 ≤ 2.6, with no swollen joints at the time of the last TCZ infusion. Patients were followed thereafter every 8 weeks for 12 months or until relapse. Relapse was defined as the presence of ≥ 1 swollen joint. Doses of methotrexate and antiinflammatory drugs were not changed during the followup period. RESULTS: Forty-five patients were analyzed, 87% were women (mean age 52 yrs, mean disease duration 14 yrs). During the 12 months of followup, 44% of patients maintained remission. Relapses occurred in 56% of patients: 14 during the first 3 months after the last TCZ administration. Retreatment using other agents achieved low disease activity or remission. CONCLUSION: Longterm clinical remission is possible in a number of patients with RA after suspension of TCZ. This effect has also been reported with other biologic agents. Additional data are required to support recommendations for discontinuing a biological agent after achieving remission.