Search

BACKGROUND: Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly diverse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and other research activities. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process. METHODS: The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre. RESULTS: To date more than 5,300 patients have been enrolled from 28 sites in Australia and New Zealand. Multiple challenges arose during the development, wh

Background: Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There are minimal data on HT in the Australian setting. Aim(s): To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital. Method(s): All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed using the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model. Result(s): A cohort of 45 patients was identified with a median age of 66 years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score >=3). R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) induction was used in 69%, with an overall response rate of 82% (complete response (CR), 75%). Sixty-one percent of these induction responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs 54%, P = 0.057) and 5-year OS (82% vs 46%, P = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction responders. Conclusion(s): Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naive at HT.Copyright © 2020 Royal Australasian College of Physicians

Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level ,1% to 2% with a ,1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received $2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD2; 30%) or retaining a low-level NPM1mut transcript (12% for $12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction ,4.4-log) at EOT.Copyright © 2021 American Society of Hematology. All rights reserved.

Background Transformation of Chronic Lymphocytic Leukaemia (CLL) or Small Lymphocytic Lymphoma (SLL) to high-grade disease (Richter's Transformation; RT) carries a poor prognosis. Despite the advent of novel therapies, published data indicates that chemoimmunotherapy remains the standard of care for RT. This project evaluated real-world outcomes in patients with RT across eight Australian centres to validate known prognostic factors, as well as identify new predictors of survival in this cohort of patients. Our aims were also to determine if prior BTK inhibitors (BTKi), BCL 2 inhibitors (BCL2i), or escalation of treatment regimen impacted these patients' outcome. Methods This was a retrospective multicentre study conducted by members of the Australasian Lymphoma Alliance in 8 centres across 4 Australian states. Consecutive patients with biopsy proven Diffuse Large B-Cell Lymphoma (DLBCL) or Hodgkin Lymphoma (HL) type RT between 2010 and 2019 were identified using institutional databases. Patients' diagnoses were confirmed by review of local pathology reports. Patients' characteristics, treatment received, and outcomes were recorded and analysed. Univariate comparisons were made using Cox regression analysis. Kaplan Meier curves were used for analysis of overall survival (OS) measured from diagnosis of high-grade disease. Results Seventy-eight patients (55 with CLL and 23 with SLL) were included in the analysis. The majority had low Rai stage at diagnosis (stage 0 in 41% of patients, 1 in 39%, 2 in 16%, 3 in 3%, and 4 in 1%). 25% had prior treatment of low-grade disease with a BTKi and 18% with a BCL2i. At the time of low-grade diagnosis, 54/78 (69%) of patients (pts) had had mutational analysis: 24% (13/54) had a 17p deletion, 78% (17/22) were IgHv unmutated, and 33% (6/18) had a TP53 mutation. Median time to transformation from CLL diagnosis was 4.8 years (range 0-24). 42% had received 2 prior lines of treatment for CLL/SLL at the time of transformation (range 0-5)

Background Transformation of Chronic Lymphocytic Leukaemia (CLL) or Small Lymphocytic Lymphoma (SLL) to high-grade disease (Richter's Transformation; RT) carries a poor prognosis. Despite the advent of novel therapies, published data indicates that chemoimmunotherapy remains the standard of care for RT. This project evaluated real-world outcomes in patients with RT across eight Australian centres to validate known prognostic factors, as well as identify new predictors of survival in this cohort of patients. Our aims were also to determine if prior BTK inhibitors (BTKi), BCL 2 inhibitors (BCL2i), or escalation of treatment regimen impacted these patients' outcome. Methods This was a retrospective multicentre study conducted by members of the Australasian Lymphoma Alliance in 8 centres across 4 Australian states. Consecutive patients with biopsy proven Diffuse Large B-Cell Lymphoma (DLBCL) or Hodgkin Lymphoma (HL) type RT between 2010 and 2019 were identified using institutional databases. Patients' diagnoses were confirmed by review of local pathology reports. Patients' characteristics, treatment received, and outcomes were recorded and analysed. Univariate comparisons were made using Cox regression analysis. Kaplan Meier curves were used for analysis of overall survival (OS) measured from diagnosis of high-grade disease. Results Seventy-eight patients (55 with CLL and 23 with SLL) were included in the analysis. The majority had low Rai stage at diagnosis (stage 0 in 41% of patients, 1 in 39%, 2 in 16%, 3 in 3%, and 4 in 1%). 25% had prior treatment of low-grade disease with a BTKi and 18% with a BCL2i. At the time of low-grade diagnosis, 54/78 (69%) of patients (pts) had had mutational analysis: 24% (13/54) had a 17p deletion, 78% (17/22) were IgHv unmutated, and 33% (6/18) had a TP53 mutation. Median time to transformation from CLL diagnosis was 4.8 years (range 0-24). 42% had received 2 prior lines of treatment for CLL/SLL at the time of transformation (range 0-5)

Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level ,1% to 2% with a ,1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received $2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD2; 30%) or retaining a low-level NPM1mut transcript (12% for $12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction ,4.4-log) at EOT.Copyright © 2021 American Society of Hematology. All rights reserved.

BACKGROUND: Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There are minimal data on HT in the Australian setting. AIMS: To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital. METHODS: All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed using the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model. RESULTS: A cohort of 45 patients was identified with a median age of 66 years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score ≥3). R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) induction was used in 69%, with an overall response rate of 82% (complete response (CR), 75%). Sixty-one percent of these induction responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs 54%, P = 0.057) and 5-year OS (82% vs 46%, P = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction responders. CONCLUSIONS: Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naïve at HT.

Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level <1% to 2% with a <1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD-; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction <4.4-log) at EOT.

BACKGROUND: Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There is minimal data on HT in the Australian setting. AIM: To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital. METHOD(S): All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed by the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model. RESULT(S): A cohort of 45 patients was identified with a median age of 66years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score >=3). R-CHOP induction was used in 69% with an overall response rate of 82% (complete response (CR), 75%). 61% of these induction-responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow-up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs. 54%, p = 0.057) and 5-year OS (82% vs. 46%, p = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction-responders. CONCLUSION(S): Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naive at HT. This article is protected by copyright. All rights reserved.

BACKGROUND: Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There is minimal data on HT in the Australian setting. AIM: To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital. METHOD(S): All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed by the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model. RESULT(S): A cohort of 45 patients was identified with a median age of 66years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score >=3). R-CHOP induction was used in 69% with an overall response rate of 82% (complete response (CR), 75%). 61% of these induction-responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow-up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs. 54%, p = 0.057) and 5-year OS (82% vs. 46%, p = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction-responders. CONCLUSION(S): Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naive at HT. This article is protected by copyright. All rights reserved.

Acute monocytic leukaemia (French-British-American classification: AML-M5b) is characterised by a predominance of cells of the monocytic lineage on bone marrow examination. Furthermore, a discerning feature is its tendency for tissue infiltration. While gum hypertrophy and hepatosplenomegaly are common, ocular involvement is rare. Here, we present a case of a 75-year-old man referred with proptosis and monocytosis - subsequently diagnosed as AML-M5b, whose disease course was distinguished by extensive tissue invasion (ocular, pulmonary, liver, spleen). Cytogenetics and molecular tests were consistent with blastic transformation of previously undiagnosed chronic myelomonocytic leukaemia, supported by the presence of long-standing, low-grade monocytosis. Notably, a BRAF V600E mutation was also detected - an oncogenic driver previously reported in de novo and therapy-related, but not chronic myelomonocytic leukaemia-transformed, AML-M5b. While an initial response to cytoreductive treatment was observed, his tissue-invasive disease soon progressed with worsening pulmonary infiltrates, disseminated intravascular coagulation and renal failure, resulting in death.Copyright © BMJ Publishing Group Limited 2019.

Acute monocytic leukaemia (French-British-American classification: AML-M5b) is characterised by a predominance of cells of the monocytic lineage on bone marrow examination. Furthermore, a discerning feature is its tendency for tissue infiltration. While gum hypertrophy and hepatosplenomegaly are common, ocular involvement is rare. Here, we present a case of a 75-year-old man referred with proptosis and monocytosis - subsequently diagnosed as AML-M5b, whose disease course was distinguished by extensive tissue invasion (ocular, pulmonary, liver, spleen). Cytogenetics and molecular tests were consistent with blastic transformation of previously undiagnosed chronic myelomonocytic leukaemia, supported by the presence of long-standing, low-grade monocytosis. Notably, a BRAF V600E mutation was also detected - an oncogenic driver previously reported in de novo and therapy-related, but not chronic myelomonocytic leukaemia-transformed, AML-M5b. While an initial response to cytoreductive treatment was observed, his tissue-invasive disease soon progressed with worsening pulmonary infiltrates, disseminated intravascular coagulation and renal failure, resulting in death.Copyright © BMJ Publishing Group Limited 2019.