Challenges in Administering Salvage Therapy and Outcomes of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A LMIC Real-World Study.

Standard therapy for patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL) involves salvage chemotherapy followed by autologous hematopoietic stem cell transplant. However, information regarding the number of patients receiving salvage therapy and associated factors is not available from low/middle income countries (LMICs). All patients treated at our center with RR DLBCL from 2016 to 2021 were included in the study. Univariate and multivariate analyses was performed to find factors associated with the lack of receipt of salvage chemotherapy. Eighty-five patients were included in the study. Most patients had primary refractory disease (69.4%). Only 26 patients received standard salvage therapy, while the others (N = 59) received metronomic/palliative oral therapy. On univariate analysis, patients with an annual income below India's Gross National Income per capita (p = 0.014), an education level below Class XII (p = 0.025), Stage III/IV disease at relapse (p = 0.018) and CNS relapse (p = 0.027) were more likely to receive palliative therapy. Conversely, patients with a late relapse were more likely to receive salvage therapy (p = 0.001). On multivariate analysis, patients with Stage III/IV relapse (p = 0.030) and an education level less than Class XII (p = 0.012) were more likely to receive palliative therapy, while patients with a late relapse (p = 0.001) were more likely to receive salvage therapy. Patients who received salvage therapy had a longer Median OS than those who received palliative therapy (p < 0.001). Timing of relapse, stage at relapse and educational status of the patient are significant factors affecting access to effective therapy for patients with RR DLBCL in LMICs.

The frequency and clinical outcome of mono-hit and multi-hit TP53 aberrations in newly diagnosed multiple myeloma.

We investigated the frequency and outcome of mono-hit and multi-hit TP53 aberrations [biallelic or ≥1 TP53 mutations (TP53mut) or TP53mut with variant allele frequency (VAF) ≥55%] in an Indian cohort of newly diagnosed multiple myeloma (NDMM) patients. We employed fluorescence insitu hybridisation (FISH; n=457) and targeted next-generation sequencing (NGS; n=244) on plasma cell-enriched samples. We also studied the impact of TP53mut in cases with and without TP53 deletions (TP53del). In our cohort with a median age of 60 years, TP53del and TP53mut were seen in 12.9% (n=59/457; 14-95% cells) and 10.2% (n=25/244; 30 variants; VAF 3.4-98.2%; median 38.2%) respectively. Mono-hit and multi-hit-TP53 aberrations were observed in 10.2% and 7.8%, respectively. Compared to TP53-wild-type (TP53wt), mono-hit and multi-hit TP53 aberrations were associated with significantly poorer progression-free survival (PFS) (22.6 vs 12.1 vs 9.5 months; p=0.004) and overall survival (OS) [not reached (NR) vs 13.1 vs 15.6 months respectively; p=0.024]. However, multi-hit TP53 did not significantly differ in OS/PFS compared to mono-hit cases. Compared to TP53wt, PFS and OS were significantly poorer in patients with TP53mut only (9.5 vs 22.6 months and 12.1 months vs NR, respectively; p=0.020/0.004). TP53mut retained its significance even in the presence of any Revised International Staging System (HR 2.1; 95% CI 1.1-3.8; p=0.015) for OS. The detection of additional cases with TP53 aberrations, as well as poor survival associated with the presence of mutation alone, supports TP53mut testing in NDMM at least in patients without TP53del and other high-risk cytogenetic abnormalities.

Simultaneous Liver and Kidney Transplantation in a Patient With Telomere Biology Disorder: A Case Study.

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.

GVHD relapse-free survival after peripheral blood hematopoietic cell transplantation for hematologic malignancies.

The preferred choice for hematopoietic cell transplantation (HCT) donors in India is a matched related donor (MRD) followed by a haploidentical (haplo) donor for patients with hematological malignancies. International data in the haplo-HCT setting is mainly using bone marrow as a source. Almost all HCTs in India use peripheral blood stem cells (PBSC), which increases the risk of graft-versus-host disease (GVHD). In this single-center prospective study from 2017 to 2021, we sought to compare these outcomes prospectively in adult patients with hematological malignancies. Patient, disease, donor, and HCT details were prospectively recorded. GVHD prophylaxis included cyclosporine + methotrexate in MRD-HCT and post-transplant cyclophosphamide (PTCy) based in haplo-HCT. The primary endpoint GVHD relapse-free survival (GRFS) was defined as the time post-HCT without any of the following events: grade III-IV acute GVHD, chronic GVHD requiring systemic immunosuppressive treatment, disease relapse, or death from any cause. A total of 41 MRD and 33 haplo-HCT recipients were included in the study. Both cohorts were matched for age, sex, diagnosis, disease risk index, donor age, sex and CMV mismatches, and CD34 counts. A lower proportion of MRD-HCT recipients than haplo-HCT received myeloablative conditioning (39% vs. 76%, p = 0.002). There was no difference in the cumulative incidence of grade III-IV acute GVHD (16% vs. 27%, p = 0.2) or moderate-to-severe chronic GVHD (58% vs. 71%, p = 0.5). The one-year GRFS was not significantly different (53% vs. 38%, p = 0.2), with median GRFS of 420 and 274 days. The relapse incidence (22% vs. 19%, p = 0.6) and non-relapse mortality (25% vs. 35%, p = 0.4) did not differ. There was no difference in overall survival at one year (60% vs. 52%, p = 0.3). Despite a higher proportion of myeloablative conditioning in the haplo-HCT cohort, all outcomes, including GRFS, were comparable to those of the MRD-HCT cohort. This should encourage patients without an MRD to undergo haplo-HCT.

Factors Impacting Return to Work/School among Hematopoietic Cell Transplantation Survivors in India.

Introduction: While there are data about return to work after hematopoietic cell transplantation (HCT) in survivors from resource-rich regions, similar data from resource-challenged settings are scarce. This study assessed the incidence of and factors affecting return to work/school (RTW) among HCT survivors in India. Methods: This single-center cross-sectional study was conducted at the long-term follow-up (LTFU) clinic of a large-volume HCT center during 2022-2023. HCT survivors surviving beyond four months were included after obtaining informed consent. Patients' sociodemographic, disease, HCT, and work details were recorded. The factors affecting RTW were evaluated using univariate (ANOVA) and logistic regression analyses. Results: A total of 126 HCT survivors participated in the study. Of these, 34 (27%) did not RTW, 47 (37%) returned to part-time work, and 45 (36%) returned to full-time work at a median of more than three years post-HCT. The three groups did not significantly differ in age, sex, or marital status. The univariate analysis revealed that education, pre-HCT job status, income, and conditioning intensity were significantly associated with RTW. Logistic regression analysis revealed that survivors with a higher (taxable) income were more likely to RTW than those with a lower (non-taxable) income (OR 3.5; CI 1.2-10.2, p=0.01). Survivors with a desk job were more likely to RTW than those who were unemployed/retired or students (OR 4.5; CI 1.1-18.0, p=0.03). Conclusion: Socioeconomic factors, like pre-HCT job status and income, were significantly associated with post-HCT RTW. Therefore, there is a need to integrate multidisciplinary RTW programs for HCT survivors in India.

No role of common NOD2 gene variants in predicting sepsis related outcomes in Indian patients undergoing hematopoietic stem cell transplant.

Background: High-risk single nucleotide polymorphisms (SNPs) in nucleotide-binding oligomerization domain-2 (NOD2) gene are associated with high susceptibility for infections and inflammation due to risk of inappropriate cytokine production and NF-κB activation. We studied the incidence of three high-risk NOD2 gene SNPs (8, 12 and 13) among BM-transplant (BMT) recipients. Methods: Sequential patients undergoing BMT over 1-year period were prospectively studied. Patients were tested with MspI/HhaI or NlaIV restriction-endonucleases (Euryx, Gdansk, Poland) for NOD2 gene SNPs 8, 12, and 13, respectively. Regimen-related organ toxicity was graded using the Seattle-Bearman criteria. Results: Forty patients were enrolled, their median age was 38 years (range 3-64), and 52.5% were males. Twenty patients each (50%) underwent autologous and allogeneic BMT. Majority of the patients (n = 38, 95%) developed febrile-neutropenia in the post-transplant period and 4 patients died due to overwhelming sepsis within day +100. Acute graft-versus-host disease (GVHD) [grade I-II (n = 3) and grade III-IV (n = 6)] was observed in 9/20 allogeneic HSCT recipients. None of our 40 patients showed presence of any of the three NOD2 gene SNPs. Conclusion: The 3 commonly observed high risk SNPs (8,12, and 13) of NOD2 genes were not present in study population. It is quite likely that due to geographical and racial variations these polymorphisms are completely absent in North India. NOD2 gene is highly diverse and polymorphic variants can be absolutely different in various populations. Larger studies targeting sequencing of the whole NOD2 gene can convincingly rule out or confirm the role of NOD2 gene variants in Indian population.

Factors associated with thrombo-hemorrhagic deaths in patients with Acute Promyelocytic leukemia treated with Arsenic Trioxide and all-trans retinoic acid.

Acute Promyelocytic Leukemia (APL) is associated with excellent long-term outcomes. However, early mortality due to coagulopathy remains a challenge. In this study we examined the bleeding and thrombotic manifestations, as well as incidence of Early Death secondary to thrombosis/hemorrhage (ED-TH) in patients with APL. Early death (ED) was defined as death occurring within 30 days of induction therapy. Two-hundred forty-eight patients were included in the study. Overall, 57 patients had evidence of a major bleed/thrombosis at presentation or during induction therapy, including 44 patients with a major bleed, 8 patients with thrombosis and 5 patients with both evidence of thrombosis and a major bleed. Forty patients (16.1%) had ED, of which 21 had ED-TH. The cumulative incidence of death due to thrombo-hemorrhagic complications at 30 days was 8.4%. On univariate analysis, increasing Prothrombin time (PT)(p-<0.001), white blood cell count (p < 0.001) and activated Partial thromboplastin time (aPTT) (p < 0.001) were statistically significantly associated with increased risk of ED-TH. However, on multivariate analysis, only increasing PT (p-0.025) and aPTT (p-0.041) were significantly associated with increased risk of ED-TH.

Pregnancy and long-term outcomes of female patients with chronic myeloid leukemia on tyrosine kinase inhibitors who experienced unplanned pregnancies.

PURPOSE: Despite the general recommendation to avoid Tyrosine Kinase Inhibitors (TKIs) for Chronic Myeloid Leukemia (CML) during pregnancy, unplanned pregnancies still occur, particularly among female patients residing in low- and middle-income countries (LMICs). We aimed to investigate the outcomes of pregnancy, foetal development, and disease progression among female CML patients in chronic phase (CML-CP) undergoing TKI therapy who encountered unplanned pregnancies in a tertiary care hospital in northern India. METHODS: We conducted a retrospective analysis of all pregnancies in female CML-CP between January 2002 and December 2022 at our hospital. Patients were included if they had a confirmed diagnosis of CML-CP, were receiving TKI therapy during conception, and had available medical records. We analysed the data on pregnancy outcomes, foetal development, and disease progression through a review of medical records. RESULTS: We identified 36 pregnancies in female CML-CP patients on TKI therapy during the study period, with 33 (91.7%) being unplanned. Sixteen pregnancies (48.5%) were conceived at less than major molecular remission (MMR) status. Twelve pregnancies (36.4%) were electively terminated, 4 (12.1%) had miscarriages, and, 17 (51.5%) pregnancies resulted in childbirth. Out of the 17 childbirths, 10 were full-term deliveries, and 7 were preterm deliveries. Twin pregnancies had a high incidence (18.2%). Among the 21 pregnancies that were not electively terminated, TKI was stopped at the first pregnancy detection in 14 pregnancies, while imatinib was continued throughout 7 pregnancies. Patients who discontinued TKI had a higher but statistically non-significant incidence of adverse pregnancy outcomes compared to those who continued imatinib throughout pregnancy (64.2% vs. 28.6%, p = 0.18). Additionally, the risk of long-term disease progression among patients who discontinued TKI during pregnancy and those who continued imatinib throughout pregnancy was 21.4% and 16.7% (p = 0.9), respectively. The risk of long-term disease progression was significantly increased in those persistently at less than MMR pre- and post-gestation (p = 0.0002). CONCLUSION: Our findings suggest that continuing imatinib therapy during pregnancy, may be a reasonable option for CML patients residing in low- and middle-income countries to reduce the risk of disease progression and adverse pregnancy outcomes. Patients persistently at less than MMR levels pre- and post-gestation should be closely monitored for the risk of long-term disease progression. Further studies with larger sample sizes are needed to confirm these results.

Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients.

BACKGROUND: Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post-AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries. MATERIALS AND METHODS: We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient-specific, disease-specific, and transplant-specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen-related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100. RESULTS: Ninety-five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33-68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4-144). Eighty-nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile-associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9-14) and 12 days (range 9-23), respectively. The median duration of hospital stay was 16 days (range 9-29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant-related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10 vs. day +11) and platelet engraftment (day +11 vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression-free survival of the study population at 5 years were 72.7% and 64.8%, respectively. CONCLUSION: This study shows that the incidence of infections and TRM are higher in MM patients from lower-middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis.

Utility of eGVHD App for bedside GVHD assessment in a high-volume BMT center.

Assessing acute and chronic graft-versus-host disease (GVHD) is challenging because there are several classification systems. The European Society for Blood and Marrow Transplantation and the Center for International Bone Marrow Transplantation Registry task force recommends using the eGVHD application (App) to score acute GVHD according to the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria and chronic GVHD according to the National Institutes of Health 2014 criteria. We prospectively used the eGVHD App at each follow-up visit in a large-volume bone-marrow transplant center in India from 2017 to 2021. We retrospectively evaluated the discrepancy in scoring GVHD severity by physicians not using the App from the same patient charts. The App user satisfaction and experience were recorded using the technology acceptance model (TAM) and the Post-Study System Usability Questionnaire (PSSUQ). In 100 consecutive allogeneic hematopoietic cell transplantation recipients, there was more discrepancy in scoring the severity of chronic GVHD (38%) than acute GVHD (9%) without using the App. The median TAM and PSSUQ scores were six (IQR:1) and two (IQR:1), respectively, indicating high perceived usefulness and user satisfaction. The eGVHD App is an excellent learning tool for hematology/BMT fellows and helps manage GVHD in high-volume BMT centers.

Role of fluoroquinolone prophylaxis in allogeneic hematopoietic cell transplantation in regions with a high prevalence of fluoroquinolone resistance.

Introduction: The role of fluoroquinolone (FQ) prophylaxis in preventing gram-negative bacilli (GNB) bacteremia, graft-versus-host disease (GVHD), and overall survival (OS) after allogeneic hematopoietic cell transplantation (allo-HCT) is debatable and may differ in settings with low and high prevalences of FQ resistance. In this study, we aimed to answer this question in regions with high FQ resistance. Methods: This single-center retrospective study included all consecutive allo-HCT recipients aged ≥12 years from 2012 to 2021. Allo-HCT recipients until 2016 were administered FQ prophylaxis (levofloxacin). After 2016, the institutional protocol was modified to no antibiotic prophylaxis. Data were retrieved from patient records for disease and transplant characteristics, the incidence of GNB bacteremia, duration of parenteral antibiotics, hospitalization duration, acute GVHD, and OS. Results: A total of 135 allo-HCT recipients (43 in the FQ-prophylaxis cohort and 92 in the no-antibiotic prophylaxis cohort) were analyzed in this study. The two cohorts were matched for age (median, 26 vs. 24.5 years; p = 0.8). The no-antibiotic prophylaxis cohort had a higher proportion of malignant diagnoses (80% vs. 58%, p = 0.01), haploidentical transplants (46% vs. 14%, p = 0.004), and posttransplant cyclophosphamide exposure (46% vs. 14%, p = 0.003) than did the FQ cohort. Despite this, the incidence of GNB bacteremia was not significantly different between the two cohorts (37% vs. 34%, p = 0.6). There were no differences in parenteral antibiotic use or hospitalization duration, as well as the incidence of acute GVHD (53% vs. 53%, p = 0.3). The 1-year OS was similar between the two cohorts (66% vs. 67%, p = 0.6). Conclusion: This study shows that FQ prophylaxis did not affect the incidence of GNB bacteremia, parenteral antibiotic use, hospitalization duration, acute GVHD, and OS post-allo-HCT.

Randomized Controlled Trial of Isha Kriya versus Observation to Improve Quality of Life in Hematopoietic Cell Transplantation Recipients.

Hematopoietic cell transplantation (HCT) impacts recipients' quality of life (QoL). Few mindfulness-based interventions (MBI) in HCT recipients have shown feasibility, but heterogeneous practices and outcome measures have called into question the actual benefit. We hypothesized that self-guided isha kriya, a 12-minute guided meditation based on the principles of yoga focusing on breathing, awareness, and thought, as a mobile app would improve QoL in the acute HCT setting. This single-center, open-label, randomized controlled trial was conducted in 2021 to 2022. Autologous and allogeneic HCT recipients age ≥18 years were included. The study was approved by our Institutional Ethics Committee and registered at the Clinical Trial Registry of India, and all participants provided written informed consent. HCT recipients without access to smartphones or regular practitioners of yoga, meditation, or other mind-body practices were excluded. Participants were randomized to the control arm or the isha kriya arm at a 1:1 ratio stratified by type of transplantation. Patients in the isha kriya arm were instructed to perform the kriya twice daily from pre-HCT to day +30 post-HCT. The primary endpoint was QoL summary scores as assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) questionnaires. The secondary endpoints were the differences in QoL domain scores. The validated questionnaires were self-administered before the intervention and at days +30 and +100 post-HCT. The analysis of endpoints was done on an intention-to-treat basis. Domain and summary scores were calculated for each instrument as recommended by the developers. A P value < .05 was considered to indicate statistical significance, and Cohen's d effect size was used to determine clinical significance. A total of 72 HCT recipients were randomized to the isha kriya and control arms. Patients in the 2 arms were matched for age, sex, diagnosis, and type of HCT. The 2 arms showed no differences in pre-HCT QoL domain, summary, and global scores. At day +30 post-HCT, there was no difference between the arms in the mean FACT-BMT total score (112.9 ± 16.8 for the isha kriya arm versus 101.2 ± 13.9 for the control arm; P = .2) or the mean global health score (global mental health, 45.1 ± 8.6 versus 42.5 ± 7.2 [P = .5]; global physical health, 44.1 ± 6.3 versus 44.1 ± 8.3 [P = .4]) in the 2 groups. Similarly, there were no differences in physical, social, emotional, and functional domain scores. However, the mean bone marrow transplantation (BMT) subscale scores, which addresses BMT-specific QoL concerns, were statistically and clinically significantly higher in the isha kriya arm (27.9 ± 5.1 versus 24.4 ± 9.2; P = .03; Cohen's d = .5; medium effect size). This effect was transient; mean day +100 scores showed no difference (28.3 ± 5.9 versus 26.2 ± 9.4; P = .3). Our data indicate that the isha kriya intervention did not improve the FACT-BMT total and global health scores in the acute HCT setting. However, practicing isha kriya for 1 month was associated with transient improvement in the FACT-BMT subscale scores on day +30 but not on day +100 post-HCT.

Feasibility of treatment-free remission with generic imatinib: Results of generic imatinib-free trial-in-chronic myeloid leukaemia-chronic phase study.

Background & objectives: Both innovator and generic imatinib are approved for the treatment of Chronic Myeloid Leukaemia-Chronic phase (CML-CP). Currently, there are no studies on the feasibility of treatment-free remission (TFR) with generic imatinib. This study attempted to determine the feasibility and efficacy of TFR in patients on generic Imatinib. Methods: In this single-centre prospective Generic Imatinib-Free Trial-in-CML-CP study, twenty six patients on generic imatinib for ≥3 yr and in sustained deep molecular response (BCR ABLIS ≤0.01% for more than two years) were included. After treatment discontinuation, patients were monitored with complete blood count and BCR ABLIS by real-time quantitative PCR monthly for one year and three monthly thereafter. Generic imatinib was restarted at single documented loss of major molecular response (BCR ABLIS>0.1%). Results: At a median follow up of 33 months (interquartile range 18.7-35), 42.3 per cent patients (n=11) continued to be in TFR. Estimated TFR at one year was 44 per cent. All patients restarted on generic imatinib regained major molecular response. On multivariate analysis, attainment of molecularly undetectable leukaemia (>MR5) prior to TFR was predictive of TFR [P=0.022, HR 0.284 (0.096-0.837)]. Interpretation & conclusions: The study adds to the growing literature that generic imatinib is effective and can be safely discontinued in CML-CP patients who are in deep molecular remission.

Clinical Features and Outcomes of Patients with Double-Hit/Triple-Hit Multiple Myeloma Detected at Relapse.

Introduction: mSMART classifies high-risk Multiple Myeloma patients into Double Hit and Triple Hit Myeloma (DH/THM) on the basis of the number of high-risk cytogenetic abnormalities detected. We aimed to study the clinical profile and outcomes of patients with DH/THM detected at relapse in a real-world setting. Methods: The case records of all relapsed multiple myeloma patients with DH/THM diagnosed between January 2018 and December 2020 were identified and information regarding baseline characteristics, therapy and outcomes was noted. Results: Seventeen patients were diagnosed with DH/THM at relapse during the study period. Twelve patients (70.6%) were in first relapse, while 3 patients were diagnosed at second relapse and 1 patient each at 3rd and 5th relapse respectively. The most common cytogenetic combination was IgH-FGFR3 translocation with gain of 1q (seen in 10 patients; 58.8%). Ten patients (58.8%) died within the first 2 months of diagnosis and 16 patients (94.1%) died during follow up (range 0-16 months). The most common cause of death was progressive/active disease (9 patients, 56.3%). Discussion: The outcome of DH/THM at relapse is associated with an aggressive presentation and poor outcomes in the real-world setting. These patients are candidates for early aggressive or novel therapy or clinical trials.

Long-term real-world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all-trans retinoic acid without chemotherapy-a retrospective, single-centre study.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high-risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate- and high-risk disease received a further 2 years of maintenance with ATRA, 6-mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow-up. The mean (SD) estimated 5-year event-free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5-year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long-term outcomes in the real-world setting.

Improving outcomes for high-risk DLBCL: a pilot study looking at the role of fractionated cyclophosphamide with RCHOP chemo-immunotherapy (SCUBA-1 trial).

The outcomes for patients with high-risk DLBCL are suboptimal, especially in Low-middle income countries in comparison to published data from the western world. Most newer therapies aimed at improving outcomes are either unavailable or out of reach for the majority of patients in low-middle income countries. Cyclophosphamide is an easily available and accessible drug that forms the backbone for therapy for DLBCL. We conducted a single-center, open-label randomized pilot study comparing standard RCHOP to RCHOP with fractionated cyclophosphamide (RfCHOP) in patients with newly diagnosed, high-risk DLBCL. Fifty-five patients were randomized- 28 to RfCHOP and 27 to the RCHOP arm. RfCHOP was associated with a higher complete response rate than RCHOP at the end of 6 cycles of therapy (81.2% vs. 59.3%; p-0.062). Grade III/IV adverse events were comparable in both arms with the use of prophylactic GCSF in the RfCHOP arm. At a median follow-up of 22 months, the Median EFS and OS was not reached in either arm. RfCHOP may represent a therapeutic option for patients with newly-diagnosed, high-risk DLBCL, especially in Low-middle income countries. Larger studies are required to confirm these findings.