Hematologic Response Research Articles

Long-term safety and efficacy of ropeginterferon alfa-2b in Japanese patients with polycythemia vera.

Ropeginterferon alfa-2b (ropegIFN), a new-generation interferon-based agent, has been approved in Japan for patients with polycythemia vera (PV) who are ineligible for or respond inadequately to conventional treatment. However, long-term outcomes with ropegIFN in Japanese patients have not been reported. This extension of a phase2 study of ropegIFN in Japanese patients with PV aimed to determine its long-term safety/efficacy, and changes over time in JAK2 V617F allele burden. Here, we report data from the phase2 study and subsequent extension over a period of 36months. The primary endpoint was the complete hematologic response (CHR) maintenance rate without phlebotomy (hematocrit value < 45% without phlebotomy during the previous 12weeks, platelet count ≤ 400 × 109/L, and white blood cell count ≤ 10 × 109/L). The CHR maintenance rates were 8/27 (29.6%), 18/27 (66.7%), and 22/27 (81.5%) at 12, 24, and 36months, respectively. No thrombotic or hemorrhagic events occurred. The median allele burden change from baseline was - 74.8% at 36months. All patients experienced adverse events; 25/27 (92.6%) experienced adverse drug reactions (ADRs), but no serious ADRs or deaths occurred. This interim analysis demonstrated the safety and efficacy of ropegIFN over 36months in Japanese patients with PV.

Belantamab Mafodotin in Relapsed/Refractory AL Amyloidosis: Real-World Multi-Center Experience and Review of the Literature

Introduction: Treatment for relapsed/refractory AL amyloidosis (AL) is an unmet need. The safety and efficacy of belantamab mafodotin (BLM) in multiple myeloma are known, whereas in AL data are limited. Methods: We report a multi-center cohort of AL patients receiving BLM, and review all previous data on BLM therapy in AL. Results: Twelve patients with a median of 3 (range 2–9) prior lines of therapy were included. The overall hematological response rate (ORR) was 75% (9/12), including 5 complete responses. Six of the 10 evaluable patients had organ responses. The median event-free survivals/overall survivals were 22.3 and 28.8 months, respectively. Grade 3 toxicities were mostly infections and keratopathy, occurring in 7/12 (58%). Hematological toxicities were rare. No grade 4/5 toxicities occurred. The review of the previous series reveals BLM provides an ORR of 60–83% with similar rates of corneal toxicity. Conclusion: BLM, being an off-the-shelf therapy, with acceptable toxicity even in frail patients, may be a valuable option in AL, with a high ORR, and a signal for durable responses and high-quality organ responses.

The Importance of Kidney Response over Hematologic Response in Predicting Kidney Outcomes in AL Amyloidosis

The Importance of Kidney Response over Hematologic Response in Predicting Kidney Outcomes in AL Amyloidosis

Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma With Deletion 17p

Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and measurable residual disease (MRD) status postauto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10-5 cells. One hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34 to 83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR, and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR, and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1 to 199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75 to 4.72], P < .001), while MRD negative CR post-transplant (0.35 [0.18 to 0.68], P = .002) and maintenance therapy (0.46 [0.27 to 0.77], P = 0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18 to 4.17], P = 0.013) and the presence of t(4;14) (2.55 [1.09 to 5.95], P = 0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23 to 0.94], P = 0.034) was associated with better OS. This study affirms del(17p) as a high-risk abnormality with unfavorable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.

Outcomes of Dose Escalation of Imatinib in Chronic Myeloid Leukemia Patients: A Retrospective Analysis From an Indian University Teaching Hospital.

Chronic myeloid leukemia (CML) treatment in low- and middle-income countries faces significant financial and logistical constraints. In scenarios where second-line tyrosine kinase inhibitors (TKIs) are unavailable or unaffordable, dose escalation of imatinib provides an alternative. This study evaluates the efficacy, safety, and progression-free survival (PFS) outcomes of dose escalation of imatinib in CML patients who experienced suboptimal response or progression on standard doses. A retrospective analysis of 123 CML patients treated at an Indian university teaching hospital from 2013 to 2016 was conducted. Patients who showed progression on a 400 mg dose of imatinib were escalated to 600 mg, and further to 800 mg if required. Demographic data, progression, and toxicity were analyzed. Out of 123 patients, 78 (63.4%) showed a complete hematologic response after dose escalation. The median PFS was 48 months, with a three-year PFS rate of 67%. Notable toxicities included Grade 3/4 neutropenia in 15% and gastrointestinal disturbances in 12%. Comparatively, studies suggest that switching to a second-line TKI in similar settings results in a higher PFS; however, our findings underscore that dose escalation of imatinib remains a viable alternative when financial constraints limit access to second-line therapies. In resource-constrained settings, dose escalation of imatinib can be an effective strategy for managing CML patients who progress on standard doses.

Lactational performance and hematological effects of capsaicin supplementation in dairy cows: A meta-analysis

A meta-analysis was performed to investigate the effects of capsaicin (CAP) on lactational performance and blood chemistry and cell counts in dairy cattle. The database comprised 11 peer-reviewed studies published between 2011 and 2024. The overall effect of CAP, challenge (e.g., ketosis, glucose tolerance, LPS), and dose were considered explanatory variables in the analysis. Lactation performance response variables included DMI, milk yield (MY), ECM yield, feed efficiency (FE), milk components, and BW. Hematological response variables included red and white blood cell counts and blood BHB, total fatty acids, insulin, and glucose concentrations. Data were analyzed using random- and mixed-effect models in the "robumeta" package in RStudio. Milk yield was increased by 2.9% by CAP when compared with control. Capsaicin supplementation increased FE by 3.4% compared with control. Milk fat concentration and yield were also increased by CAP compared with control by 2.6% and 4.0%, respectively. Blood glucose concentrations were decreased 2.5% by CAP supplementation, whereas insulin levels were unaffected. Cows fed CAP during a challenge had higher MY and FE and tended to have lower blood glucose than their control counterparts. Overall, this analysis suggests that CAP supplementation may be directly affecting host physiology by altering glucose metabolism, but further research to define the mechanism is warranted.

Assessing the predictive value of pre- and post-operative inflammatory markers in patients undergoing total knee arthroplasty

Background and objectiveTotal Knee Arthroplasty (TKA) has proven highly effective in improving quality of life for patients with severe knee conditions. Despite advancements, surgical complications such as periprosthetic joint infections (PJIs) pose risks. The potential predictive value of pre- and post-operative inflammatory markers like neutrophil-to-lymphocyte ratio (NLR), D-dimer, and albumin levels on surgical outcomes is garnering attention. There is a growing interest in leveraging these markers to enhance patient selection and outcome prediction in the context of TKA.Focusing on the natural course of these markers, and the incidence of PJIs and to refine perioperative care strategies, improve patient outcomes, and identify high-risk patients for targeted intervention.MethodsThe study included 94 patients who underwent total knee arthroplasty (TKA) between 2019 and 2023. Blood tests were conducted before surgery and at 1, 3, 7, and 15 days after surgery to assess various parameters including white blood cell count, neutrophils, lymphocytes, platelets, hemoglobin, C-reactive protein, D-dimers, total protein, albumin, and total cholesterol values and ratios.ResultsFollowing total knee arthroplasty (TKA), key observations in blood markers included a sharp rise in white blood cell (WBC) counts from 5.81 to 10.22 (*10^9/L) on the first day post-surgery, with levels returning close to preoperative values by day-15. Neutrophil counts similarly increased from 3.46 to 8.50 (*10^9/L) on day-1, decreasing to 4.01 by day-15. Hemoglobin levels significantly decreased from 115.70 g/L to 90.62 by day-3 before improving to 100.30 by day-15. C-reactive protein (CRP) levels also saw a significant rise from 6.15 mg/L to a peak of 47.07 on day-3, then reducing to 10.55 by day-15, indicating a response to inflammation.ConclusionFollowing total knee arthroplasty (TKA), a significant initial postoperative increase in white blood cell count, neutrophils, and C-reactive protein levels, indicative of an acute inflammatory response, before returning towards baseline values by day 15. Hemoglobin levels displayed a notable dip post-surgery, gradually improving by the study’s end. These patterns emphasize the dynamic nature of inflammatory and hematological responses after TKA, highlighting their potential role in predicting surgical outcomes and guiding postoperative care.

Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia.

Hydroxyurea (HU) constitutes the first-line treatment in most patients with essential thrombocythemia (ET), but criteria for changing therapy are not clearly established. The prognostic value of complete hematological response (CHR) and resistance/intolerance to HU was assessed in 1080 patients from the Spanish Registry of ET, classified according to revised IPSET-Thrombosis stratification (Very low- n = 61, Low- n = 83, Intermediate- n = 261, and High-risk n = 675). With a median therapy duration of 5 years, CHR was registered in 720 (67%) patients (1-year probability 51%) and resistance/intolerance in 219 (20%) patients (5-years probability 13%). After correction by other risk factors, High-risk patients achieving CHR showed a reduced risk of arterial thrombosis (HR: 0.35, 95%CI: 0.2-0.6, p = 0.001) and a trend towards lower risk of venous thrombosis (HR: 0.45, 95%CI: 0.2-1.02, p = 0.06) whereas no association was observed for intermediate- or low-risk patients. In comparison with non-responders, intermediate- and high-risk patients achieving CHR had longer survival and lower myelofibrosis incidence. Development of resistance/intolerance to HU, mainly cytopenia, was associated with higher probability of myelofibrosis but no effect on survival or thrombotic risk was demonstrated. In conclusion, CHR with HU is associated with better outcomes and might be an early indicator for selecting candidates to second-line clinical trials.

Molecular profiling of pre- and post- 5-azacytidine myelodysplastic syndrome samples identifies predictors of response.

Treatment with the hypomethylating agent 5-azacytidine (AZA) increases survival in high-risk (HR) myelodysplastic syndrome (MDS) patients, but predicting patient response and overall survival remains challenging. To address these issues, we analyzed mutational and transcriptional profiles in CD34+ hematopoietic stem/progenitor cells (HSPCs) before and following AZA therapy in MDS patients. AZA treatment led to a greater reduction in the mutational burden in both blast and hematological responders than non-responders. Blast and hematological responders showed transcriptional evidence of pre-treatment enrichment for pathways such as oxidative phosphorylation, MYC targets, and mTORC1 signaling. While blast non-response was associated with TNFa signaling and leukemia stem cell signature, hematological non-response was associated with cell-cycle related pathways. AZA induced similar transcriptional responses in MDS patients regardless of response type. Comparison of blast responders and non-responders to normal controls, allowed us to generate a transcriptional classifier that could predict AZA response and survival. This classifier outperformed a previously developed gene signature in a second MDS patient cohort, but signatures of hematological responses were unable to predict survival. Overall, these studies characterize the molecular consequences of AZA treatment in MDS HSPCs and identify a potential tool for predicting AZA therapy responses and overall survival prior to initiation of therapy.

Hematological and performance adaptations to altitude training (2,320m) in elite middle-distance and distance swimmers.

Elite swimmers often schedule altitude training camps ahead of major events in an attempt to maximize performance. However, the relationships between altitude-induced hematological changes, markers of training adaptation, and performance changes in such context are unclear. This study assessed hematological status, markers of daily adaptation, and swimming performance in elite middle-distance and distance swimmers during a 22-day altitude training camp at 2,320m, 2weeks prior to World Championship qualification competition. Venous blood was obtained and total hemoglobin mass (tHbmass) measured (CO rebreathing) in 7 elite swimmers (4 females, 3 males) 8days before and on day 22 of the altitude camp. Resting heart rate, peripheral oxygen saturation, urinary specific gravity, body mass, fatigue and self-reported sleep duration and quality were monitored daily during the altitude camp. Swimming performance was assessed through a standardized set (6 sets of 4 maximal repetitions of 100m front crawl) on days 3, 10 and 17 of the camp, and at sea level competitions (200m-1,500m) immediately after the camp, and 2weeks later. tHbmass (+5.6 ± 3.3%; range: 2.1%-11.0%; p < 0.05), red blood cell count, hemoglobin concentration, hematocrit increased at the end of the training camp (p < 0.05). Performance at altitude improved throughout the camp (+1.4 ± 0.4%; range: 0.7%-2.5%; p < 0.05). No significant relationship was noted between hematological changes, the change in altitude performance and any of the monitored daily markers of adaptation during the camp. Compared to the swimmers' previous personal best, competition performances did not improve immediately (2.5% ± 1.9% slower times) and 2weeks after altitude (1.2% ± 1.4% slower times). The 22-day altitude training camp at 2,320m was beneficial for elite swimmers' tHbmass, hematological status and performance at altitude, but these benefits did not clearly translate into enhanced sea level performance immediately after or 2weeks later. The present study confirms the large inter-individual variability in hematological responses to altitude training, and that the improvement in performance at altitude and sea level may depend on factors other than the increase in tHbmass alone.

Impact of Chaetomorpha aerea-enriched diet on growth, feed utilization, and haemato-immunological responses in Clarias batrachus challenged with Aeromonas hydrophila

The bacteria Aeromonas hydrophila, which causes motile Aeromonas septicemia (MAS), is dangerous to aquaculture because it affects the fish's well-being and production. As the aquaculture industry seeks sustainable and effective methods to enhance fish immunity and growth, natural supplements such as marine algae have gained attention. This study explored the potential benefits of incorporating the green marine algae Chaetomorpha aerea into the fish diet, focusing on disease resistance, growth, feed utilization, and hematological and immunological responses. Five diets were prepared, varying concentrations of C. aerea (0 control, T1: 1 g/kg; T2: 2 g/kg: T3: 5 g/kg: and T4: 10 g/kg) and administered to fish over 30 days. Following the feeding trial, the fish were exposed to A. hydrophila, and their survival rates were observed for the next 14 days. The findings demonstrated that the final weight, weight gain, relative growth rate, specific growth rate, and daily growth rate were all positively impacted by a diet containing 5 g/kg of C. aerea. Additionally, fish in the 5 g/kg C. aerea group demonstrated improved feed conversion efficiency compared to the control group. While there were no significant changes in red and white blood cell counts on the initial day, serum lysozyme activity and overall resistance to infection were enhanced in fish receiving C. aerea at 2 and 5 g/kg. These results imply that C. aerea supplementation with fish supplements may be a useful immunostimulant, boosting improved health and growth in sustainable aquaculture practices.

Impacts of substituting fish meal with full-fat or defatted black soldier fly (Hermetia illucens) larvae on growth, quality, and health of Nile tilapia (Oreochromis niloticus) fingerlings

This study investigated the use of black soldier fly (Hermetia illucens) larvae (BSFL), provided in either full-fat (FBSF) or defatted (DBSF) forms, as an alternative protein source in the diet of Nile tilapia (Oreochromis niloticus) fingerlings. Specifically, the influence was assessed of BSFL on growth performance, hematological parameters, body composition, and histology. Nine diets (including the control) were formulated to be isonitrogenous (35 % crude protein) and isolipidic (6 % crude lipid), relying on fish meal as the primary protein source and gradually replacing it with BSFL meal at levels of 25 %, 50 %, 75 %, or 100 % on an equivalent protein basis, corresponding to dietary inclusion levels of 5.25 %, 10.25 %, 15.5 %, and 20.0 %, respectively. Fish with an initial mean weight ± standard deviation of 1.3 ± 0.26 g were fed for 12 weeks until the fish final weight was in the range 24.08–34.95 g. Based on the results, there were no significant (p>0.05) differences in the growth performance or feed conversion ratios among the treatments. Additionally, there were no significant differences in the hematological responses or the proximate body composition. Furthermore, 100 % substitution of fish meal with FSFL and DBSF meal caused blood congestion in the hepatopancreas region and several intraepithelial leukocytes in the intestine. There were no detrimental impacts at levels of 25 %, 50 %, and 75 % on growth performance, hematological responses, body composition, or the intestines or liver histological characteristics of the O. niloticus fingerlings. This information should provide useful guidance for the management of Nile tilapia, an economically important species.

Factors impeding organ recovery despite a deep haematological response in patients with systemic AL amyloidosis.

Patients with AL amyloidosis can have persistent organ dysfunction despite achieving a haematological complete response (hemCR). We aimed to identify factors for organ non-response among 143 patients who achieved hemCR for ≥6 months. Kidney, heart and liver non-response were observed in 40/117 (34%), 19/68 (28%) and 3/17 (18%) patients respectively. Predisposing factors varied by organ system. Kidney non-responders had more advanced organ dysfunction at diagnosis, whereas heart non-responders had disproportionately more lambda-typic amyloidogenic light chains. Most patients without an apparent reason for organ non-response had detectable residual clonal disease. The interplay of factors impeding organ recovery in AL amyloidosis is complex.

Chitosan siRNA Nanoparticles Produce Significant Non-Toxic Functional Gene Silencing in Kidney Cortices.

Chitosan shows effective nucleic acid delivery. To understand the influence of chitosan's molecular weight, dose, payload, and hyaluronic acid coating on in vivo toxicity, immune stimulation, biodistribution and efficacy, precisely characterized chitosans were formulated with unmodified or chemically modified siRNA to control for innate immune stimulation. The hemocompatibility, cytokine induction, hematological and serological responses were assessed. Body weight, clinical signs, in vivo biodistribution and functional target knockdown were monitored. Hemolysis was found to be dose- and MW-dependent with the HA coating abrogating hemolysis. Compared to cationic lipid nanoparticles, uncoated and HA-coated chitosan nanoparticles did not induce immune stimulation or hematologic toxicity. Liver and kidney biomarkers remained unchanged with chitosan formulations, while high doses of cationic lipid nanoparticles led to increased transaminase levels and a decrease in body weight. Uncoated and HA-coated nanoparticles accumulated in kidneys with functional knockdown for uncoated chitosan formulations reaching 60%, suggesting potential applications in the treatment of kidney diseases.

Eculizumab as Salvage Treatment for Thrombotic Microangiopathy After Lung Transplantation.

Thrombotic microangiopathy (TMA) is a rare complication after lung transplantation (LT) that has seldom been characterized in detail. Recent evidence has linked TMA other than primary atypical hemolytic uremic syndrome (aHUS) with hyperactivation of the complement alternative pathway. The focus of this investigation was to analyze the treatment response with eculizumab in TMA after LT. Case series where we have studied 11 patients with TMA after LT from 2 Spanish tertiary healthcare centers. Clinical data and response rates to eculizumab are provided. The main indication for lung transplant was chronic obstructive pulmonary disease (COPD) (36%) and most cases (82%) received bilateral LT. The median time to TMA diagnosis was 11.6 months (4.7-28.9) and the TMA trigger in the majority of cases (73%) was immunosuppressive drugs. Platelet and hemoglobin nadir were 58×103/µL (24-108) and 7.7g/dL (7.1-7.9), respectively. All cases presented acute kidney injury (AKI) with a median creatinine of 4mg/dL (3.2-4.8) and 54.5% required acute dialysis. Eculizumab was started after a median time of 8 days (6-14) with a median duration of 3 weeks (2-8). Complete TMA response was observed in 7 (63.6%) cases and hematologic response in 10 (90.9%). The time to hematologic and renal response was 23 days (13-29) and 28 days (14-46), respectively. TMA after LT is infrequent but potentially devastating. Our findings suggest that short cycles of eculizumab may be effective for severe TMA after LT.

Response to Single Agent Cyclosporin in Patients with Non-Severe Aplastic Anaemia.

To determine the effectiveness of cyclosporin A (CSA) monotherapy in treating patients with non-severe aplastic anaemia (NSAA). A cross-sectional observational study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan, from January 2022 till December 2023. A total of 51 patients of NSAA, classified as aplastic anaemia not satisfying criteria for severe and very severe disease as per Modified Camitta Criteria, were included. Results were evaluated in terms of survival rate (OS) and responses. Responses were assessed as complete response (CR), partial response (PR), overall response (ORR), and no response (NR) by using standard British Committee for standard Haematology (BCSH) response criteria at 3, 6, and 12 months. Out of 51 patients, 34 (67%) were males and 17 (33%) were females. Median age at the time of diagnosis was 25 (IQR 26) years. At follow-up of 12 months, OS was 86.3%. Overall response rates to cyclosporin monotherapy at 3, 6, and 12 months were 49%, 57%, and 59%, respectively. Baseline haemoglobin was associated with responses at 6 and 12 months and a significant association was found between transfusion dependency at 3, 6, and 12 months with overall survival (p = 0.01, 0.005, and 0.04, respectively). Responses at time-defined points also had significant impact on OS (3 months Plog-rank = 0.046, 6 months Plog-rank = 0.01, and 12 months Plog-rank = 0.008). Overall response rates at 3, 6, and 12 months indicate the potential of CSA as a viable treatment option, particularly in resource-constrained settings. Despite some patients experiencing treatment-related complications, CSA demonstrated a generally tolerable safety profile. Cyclosporin A, Non-severe aplastic anaemia, Survival rate, Response rate, Complete response, Partial response.

Response, complications and risk of leukemic transformation of phosphorus-32 p treatment in philadelphia-negative chronic myeloproliferative syndromes

ObjectiveDescribe our experience in treatment with Phosphorus-32 P for refractory Philadelphia negative chronic myeloproliferative syndromes or with side effects to the usual treatment, its complications and risk of leukemic transformation. Material and methodsRetrospective descriptive study including 17 patients with a diagnosis of Philadelphia-negative chronic myeloproliferative syndrome treated with Phosphorus-32 P in our hospital from January 1985 to March 2017. Indications, response to treatment, as well as early and late complications have been analyzed. ResultsOf the 17 patients treated with 32 P (11 men, 6 women; mean age 79,8 years), 6 patients had Polycythemia Vera and 11 Essential Thrombocytosis. A single dose was administered in 9 of the subjects, the rest required two or more doses due to inadequate hematological response and/or relapse. The total dose range of Phosphorus-32 P administered was 116-951 MBq (median: 236 MBq). In 14 patients treated with Phosphorus-32 P, complete or partial response was achieved in hematimetry. In 11 patients, the response was complete, established as a platelet count < 400.000/mm3 in those diagnosed with Essential Thrombocythemia and a hematocrit < 45% in cases of Polycythemia Vera. The median follow-up of patients from the date of the first treatment of Phosphorus-32 P until study completion or death was 37 months (range: 5 - 230 months). Regarding early complications, 2 cases of anemia requiring blood transfusion were observed, and 1 case of mild thrombocytopenia. No leukemic transformation was identified. ConclusionsIn our experience, treatment with Phosphorus-32 P has been a useful therapeutic option in Philadelphia-negative chronic myeloproliferative syndromes in elderly patients who showed poor tolerance and/or resistance to first-line treatment. No leukemic transformation was identified.

Prognostic impact of cytogenetic abnormalities detected by FISH in AL amyloidosis with daratumumab-based frontline therapy

AbstractWe performed an international retrospective study on 283 patients with light chain (AL) amyloidosis to investigate the prognostic impact of cytogenetic abnormalities by fluorescence in situ hybridization, when treated with frontline daratumumab–based therapy. The cytogenetic subgroups of interest were t(11;14), gain/amp(1q) (hereafter, +1q), hyperdiploidy, deletion(13q), del(17p), and myeloma high-risk (HR) translocations (t[4;14], t[14;16], or t[14;20]). The end points of interest were rate of hematologic complete response (heme-CR), very good partial response (VGPR) or better, and hematologic event-free survival (heme-EFS). The incidence of abnormalities was as follows: t(11;14), 53.4%; deletion (13q), 28.9%; +1q, 22.3%; hyperdiploidy, 19.4%; HR translocations, 6.6%; and deletion(17p), 4.5%. The heme-CR rate by cytogenetic subgroups were as follows: t(11;14) vs no t(11;14), 45.2% vs 41.8% (P=0.597); del(13q) vs no del(13q), 46.8% vs 42.8% (P=0.594); +1q vs no +1q, 30.2% vs 47.9% (P=0.022); hyperdiploidy vs no hyperdiploidy, 39.5% vs 44.9% (P=0.541); HR translocations vs none, 45.5% vs 43.1% (P=0.877); and del(17p) vs no del(17p), 50.0% vs 42.9% (P=0.658), respectively. Similarly, +1q was the only subgroup with a significantly lower VGPR or better rate (64.2% vs 79.0%; P=0.033). At a median follow-up of 19.8 months, the median heme-EFS was 49.6 months (95% CI, 24.7-not reached [NR]), and the 2-year overall survival (OS) was 80.98% (95% CI, 75.6-85.4). The presence of +1q was significantly associated with worse heme-EFS on multivariate analysis (HR 2.06, 95% CI, 1.14-3.71; P=0.017). Notably, there was no adverse prognostic impact of t(11;14) on heme-EFS or OS. In conclusion, +1q is associated with worse outcome in the daratumumab-era. Clinical trials testing novel frontline immunotherapies should be enriched in +1q to further improve outcomes in this subgroup.

Long-term outcomes of renal AL amyloidosis patients undergoing autologous stem cell transplantation: Validating the performance of the renal staging system.

Renal AL amyloidosis can be complicated by end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). In this study, we describe the long-term outcomes of renal AL amyloidosis patients undergoing autologous stem cell transplantation (ASCT) and assess the utility of the renal staging system. Retrospective study of renal AL patients (n = 697; Mayo Clinic, Boston University) who underwent ASCT between 2003 and 2020. Renal stage was assigned based on 24-h proteinuria and estimated glomerular filtration rate measurements. Renal survival was defined as the time from ASCT until initiation of RRT, while patients who were not placed on RRT were censored at their last follow-up. With a median follow-up of 10.4 years, RRT was required in 149 patients (21%). The median time from ASCT to ESRD was 3.4 years, with late events of progression to ESRD seen >10 years from ASCT. Pre-ASCT renal stage was significantly associated with the cumulative incidence of RRT: 3-year RRT rate was 3%, 10%, and 37% for renal stages I, II, and III, respectively. However, in the 2012-2020 period subset, a significant decrease in ESRD risk was noted across all renal stages (3-year RRT 0%, 5%, and 24%, respectively). In multivariate analysis, renal survival was independently associated with the pre-ASCT renal stage, lambda isotype, bone marrow plasmacytosis ≥20%, post-ASCT hematologic response, and year of ASCT. Long-term outcomes of renal AL amyloidosis treated with ASCT are presented. Renal stage reliably predicts renal outcomes in patients with AL undergoing ASCT, despite a reduction in the proportion of patients progressing to RRT in recent years.

Light chain deposition disease: pathogenesis, clinical characteristics and treatment strategies.

Light chain deposition disease (LCDD) is a rare hematologic disorder characterized by the deposition of non-amyloid monoclonal light chains in several organs. Together with renal impairment is being the primary morbidity associated with this disease. Due to its rarity, randomized clinical trials lack to explore treatment strategies and there are no approved or universally accepted standard of care treatment options. We aimed to provide a systematic summary of histological and clinical aspects of LCDD and treatment options of available literature therapies strategies. Currently, drugs used to treat multiple myeloma are recommended when LCDD patients also presented multiple myeloma. Anyway, in patients with LCDD that is not associated to multiple myeloma, haematopoietic stem cell transplantation (ASCT) and chemotherapy with thalidomide, dexamethasone, bortezomib are also recommended. In eligible patients, bortezomib-based chemotherapy followed by ASCT appears to be an effective treatment option with durable hematologic remission and organ responses. Although it appears that the patients undergoing ASCT seem to achieve deeper and durable hematologic remissions and organ responses, no statistically significant superiority can be demonstrated over non-transplant or standard chemotherapy-based approaches. As retrieved by our review, bortezomib-based therapy appears to be favorable strategy as long as no dose modification is required for renal impairment, and early hematologic responses as a recovery of renal function. Encouraging data were also demonstrated by treatment lenalidomide or melpalan based. Moreover, new myeloma treatment strategies, as monoclonal antibody Daratumumab, seem to be effective in LCDD. Instead, renal allograft is not recommended, due to high incidence of relapse.