ABSTRACT
BACKGROUND: Few Australasian autologous stem cell transplantation (ASCT) programmes perform ASCT in the private sector. Relatively little is known about ASCT outcomes in the private sector, which varies in care delivery models to the public system. AIMS: To investigate transplantation activity and survival outcomes at Icon Cancer Centre's Brisbane-based private clinical and laboratory ASCT programme over a 23-year period. METHODS: Retrospective, observational study of all adults who underwent ASCT at Icon between 1996 and 2018. Main outcome measures were transplant activity, overall survival (OS) and 100-day and 1-year transplant-related mortality (TRM). Outcomes were benchmarked against the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). RESULTS: Between 1996 and 2018, 1676 ASCT were performed in 1454 patients. From 2010 to 2018, ASCT performed at Icon contributed 40% of all South East Queensland ASCT. In the past 5 years, 21% of Icon's patients were aged ≥70 years, compared with 5% across Australasia. For the entire cohort, 100-day and 1-year TRM was 1.1% and 1.7%, respectively, while for those aged ≥70 years, it was 2.0% and 3.1%. For ASCT performed between 2014 and 2018, 100-day and 1-year TRM was 0.8% and 1.4%, which was half the TRM rates reported by the ABMTRR. The 10-year post-transplant OS at Icon was higher than the ABMTRR data, across all disease subtypes. CONCLUSION: We report excellent OS and low TRM, demonstrating the critical role of the private sector in the administration of this highly complex therapy. The Icon ASCT programme is the largest ASCT contributor in Queensland. It is inclusive of patients aged ≥70 years, demonstrating low and acceptable TRM.
Subject(s)
Hematopoietic Stem Cell Transplantation , Adult , Humans , Retrospective Studies , Transplantation, Autologous , Private Sector , Disease-Free Survival , Stem Cell TransplantationABSTRACT
Patients with post-haemopoietic stem cell transplant or chimeric antigen receptor T -cell (CAR-T) therapy face a significant risk of morbidity and mortality from coronavirus disease 2019 because of their immunosuppressed state. As case numbers in Australia and New Zealand continue to rise, guidance on management in this high-risk population is needed. Whilst we have learned much from international colleagues who faced high infection rates early in the pandemic, guidance relevant to local health system structures, medication availability and emerging therapies is essential to equip physicians to manage our patients optimally.
Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Receptors, Chimeric Antigen , Humans , Receptors, Chimeric Antigen/therapeutic use , New Zealand/epidemiology , T-LymphocytesABSTRACT
BACKGROUND: There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. AIM: To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. METHODS: Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005 and 2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematological malignancies by geographic regions. RESULTS: One thousand, five hundred and eighty-one haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data are presented for 58 major subtypes, as per the WHO diagnostic classification of tumours of haemopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematological malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100 000 ranging from 0.5 to 233.5. Our data suggest an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared with other regions. CONCLUSION: The present study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications towards developing appropriate data-driven management strategies and public health responses for haematological malignancies.
Subject(s)
Hematologic Neoplasms , Neoplasms , Adult , Humans , Male , Aged , Female , Retrospective Studies , Queensland/epidemiology , Hematologic Neoplasms/epidemiology , Neoplasms/epidemiology , IncidenceABSTRACT
Pediatric regimens have improved outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL). However, results remain inferior to children with ALL. The Australasian Leukaemia and Lymphoma Group (ALLG) ALL06 study (anzctr.org.au/ACTRN12611000814976) was designed to assess whether a pediatric ALL regimen (Australian and New Zealand Children's Haematology and Oncology Group [ANZCHOG] Study 8) could be administered to patients aged 15 to 39 years in a comparable time frame to children as assessed by the proportion of patients completing induction/consolidation and commencing the next phase of therapy (protocol M or high-risk [HR] treatment) by day 94. Minimal residual disease (MRD) response stratified patients to HR treatment and transplantation. From 2012 to 2018, a total of 86 patients were enrolled; 82 were eligible. Median age was 22 years (range, 16-38 years). Induction/consolidation was equally deliverable in ALL06 as in Study 8. In ALL06, 41.5% (95% confidence interval [CI], 30.7-52.9) commenced protocol M or HR therapy by day 94 vs 39.3% in Study 8 (P = .77). Median time to protocol M/HR treatment was 96 days (interquartile range, 87.5-103 days) in ALL06 vs 98 days in Study 8 (P = .80). Induction mortality was 3.6%. With a median follow-up of 44 months (1-96 months), estimated 3-year disease-free survival was 72.8% (95% CI, 62.8-82.7), and estimated 3-year overall survival was 74.9% (95% CI, 65.3-84.5). End induction/consolidation MRD negativity rate was 58.6%. Body mass index ≥30 kg/m2 and day 79 MRD positivity were associated with poorer disease-free survival and overall survival. Pediatric therapy was safe and as deliverable in AYA patients as in children with ALL. Intolerance of pediatric ALL induction/consolidation is not a major contributor to inferior outcomes in AYA ALL.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma , Acute Disease , Adolescent , Adult , Australia , Child , Disease-Free Survival , Humans , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Young AdultABSTRACT
Australia and New Zealand have achieved excellent community control of COVID-19 infection. In light of the imminent COVID-19 vaccination roll out in both countries, representatives of all adult and paediatric allogeneic bone marrow transplant and cellular therapy (TCT) centres as well as representatives from autologous transplant only centres in Australia and New Zealand collaborated with infectious diseases specialists with expertise in TCT on this consensus position statement regarding COVID-19 vaccination in TCT patients in Australia and New Zealand. It is our recommendation that TCT patients, should have expedited access to high-efficacy COVID-19 vaccines given that these patients are at high risk of morbidity and mortality from COVID-19 infection. We also recommend prioritising vaccination of TCT healthcare workers and household members of TCT patients. Vaccination should not replace other public health measures in TCT patients given the effectiveness of COVID-19 vaccination in TCT patients is unknown. Furthermore, given the limited available data, prospective collection of safety and efficacy data of COVID-19 vaccination in this patient group is a priority.
Subject(s)
COVID-19 Vaccines , COVID-19 , Transplant Recipients , Adult , Australia/epidemiology , COVID-19/prevention & control , Child , Consensus , Humans , New Zealand/epidemiology , Prospective Studies , VaccinationABSTRACT
We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractory T-cell lymphoma who had failed 1+ systemic therapies, treated via a compassionate access program. Endpoints assessed included response rates, toxicities, and subsequent therapies. Progression-free survival (PFS), time to next treatment (TTNT), event-free survival (EFS), overall survival (OS), and time to best response, were assessed by Kaplan-Meier analysis. The study included 31 patients, with median age 69 years. We demonstrated ORR of 35.5% (n = 11), including 4 complete responses (13%) and 7 partial responses (23%). The predicted median OS was 10 months, with EFS of 9 months, and PFS of 9 months. Median TTNT was 8 months. Mucositis was the most commonly observed toxicity. This study - the second largest real-world cohort reported to date - underscores the importance of pralatrexate in relapsed/refractory T-cell lymphoma, as well as its acceptable toxicity profile.
Subject(s)
Lymphoma, T-Cell , Neoplasm Recurrence, Local , Aged , Aminopterin/analogs & derivatives , Australia/epidemiology , Humans , Lymphoma, T-Cell/drug therapy , Neoplasm Recurrence, Local/drug therapy , Retrospective Studies , Treatment OutcomeABSTRACT
Despite their availability for over a decade, the exact nature of biosimilar medicines is still poorly understood with paucity of clear treatment guidelines for their use in clinical practice in Australia. Although hematologists have had experience with biosimilars in the setting of supportive care, with the approval of the first biosimilar rituximab in hematological malignancies, it is important to revisit this topic. To inform the use of biosimilar medicines in clinical practice, we have developed a consensus statement from an Expert Panel of Australian hematologists, oncologists, and cancer pharmacists. These recommendations address the approach to use of biosimilar products in place of the corresponding reference medicine in a number of different clinical contexts. Our recommendations are based on the premise that biosimilar medicines can be considered therapeutically equivalent to their reference brand and used in a similar way to the reference product in any approved indication. We advocate for local approaches to the provision of patient information, dispensing of the intended brand and pharmacovigilance, to be developed in consultation with local hematologists and aim to improve confidence in the appropriate use of biosimilar medicines and their expected outcomes among hematologists.
Subject(s)
Biosimilar Pharmaceuticals/therapeutic use , Hematology/methods , Australia , Biosimilar Pharmaceuticals/pharmacology , HumansABSTRACT
BACKGROUND: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies. AIMS: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards. METHODS: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed. RESULTS: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years. CONCLUSION: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.
Subject(s)
Hematopoietic Stem Cell Transplantation/mortality , Hodgkin Disease/surgery , Lymphoma, Non-Hodgkin/surgery , Multiple Myeloma/surgery , Adolescent , Adult , Aged , Disease-Free Survival , Female , Humans , Male , Middle Aged , Queensland/epidemiology , Retrospective Studies , Transplantation, Autologous , Young AdultABSTRACT
A retrospective, observational study was performed of 112 patients who underwent autologous haematopoietic stem cell transplantation (ASCT) to determine the relationship between CD34+ stem cell dose and neutrophil engraftment. Importantly, a novel approach to more accurately calculate time to neutrophil engraftment was employed. The results demonstrated that a higher CD34+ stem cell dose was associated with faster neutrophil recovery (Pâ¯<â¯0.05). CD34+ stem cell dose using actual and ideal patient body weight were both equally predictive of neutrophil engraftment as were absolute and viable CD34+ measurements. The clinical implications for this relationship are limited with an increase in CD34+ stem cell dose by 1â¯×â¯106/kg reducing the neutrophil engraftment time by only 3â¯h and 50â¯min. The median time to neutrophil recovery was 217â¯h (9 days and 1â¯h) and this relatively early engraftment time may be related to an early initiation of granulocyte colony-stimulating factor (G-CSF) on day +1 post-transplant. Female patients engrafted 17â¯h faster than their male counterparts on multi-variate analysis (Pâ¯<â¯0.05). Conditioning chemotherapy, bacteraemia, G-CSF dose/kg body weight and increasing age had no impact on time to neutrophil recovery.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/metabolism , Neutrophils/metabolism , Transplantation, Autologous/methods , Adult , Aged , Antigens, CD34/biosynthesis , Female , Humans , Male , Middle Aged , Neutrophils/cytology , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. METHODS: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300â¯mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months. RESULTS: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300â¯mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300â¯mg bid. CONCLUSION: Nilotinib 300â¯mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Adult , Aged , Dasatinib/administration & dosage , Dasatinib/adverse effects , Drug Administration Schedule , Female , Humans , Imatinib Mesylate/administration & dosage , Imatinib Mesylate/adverse effects , Male , Middle Aged , Protein-Tyrosine Kinases/antagonists & inhibitors , Treatment OutcomeABSTRACT
AIM: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) positive AML is associated with increased relapse risk and reduced overall survival (OS) compared to non-FLT3-mutated AML. The aim of this study was to evaluate the impact of allelic ratio and allogeneic transplant on outcomes in FLT3-ITD+ AML. METHODS: A retrospective study across five centers in Queensland, Australia, was conducted to examine survival outcomes and impact of FLT3-ITD allelic ratio and allograft. RESULTS: Seventy-one patients were included in the study. OS was significantly better for patients who were able to be allografted in first complete remission (CR1; 50.1 months vs 8.5 months; P = 0.0002). We did not find allelic ratio to be predictive of outcome. CONCLUSION: Transplantation in first complete remission is associated with improved outcomes for patients with FLT3+ AML. When feasible transplantation in CR1 is recommended. We do not currently recommend using allelic ratio to stratify risk unless this has been validated by local results.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Tandem Repeat Sequences/genetics , fms-Like Tyrosine Kinase 3/genetics , Adolescent , Adult , Aged , Australia/epidemiology , Disease Management , Female , Humans , Leukemia, Myeloid, Acute/epidemiology , Male , Middle Aged , Recurrence , Remission Induction , Retrospective Studies , Survival Rate , Transplantation, Homologous , Treatment Outcome , Young AdultABSTRACT
An intensive induction regimen, consisting of idarubicin and high dose cytarabine, was assessed in 19 adult patients, median age 44 years, with newly diagnosed precursor-B acute lymphoblastic leukemia (ALL). Patients achieving a complete response (CR) were given an attenuated consolidation course. The primary endpoints were induction death rate and incidence of serious non-hematological toxicity. Grades 3-4 diarrhoea occurred in 47% of patients during induction. Two patients (11%) died during induction therapy, and 2 were withdrawn due to resistant disease or prolonged marrow hypoplasia. Fifteen patients achieved CR (79%), but levels of minimal residual disease (MRD) after induction were comparable with those previously observed using a modified pediatric protocol. Overall survival at 5 years was 36.8% while leukemia-free survival was 44.1%. An intensive AML protocol used in adults with ALL resulted in substantial toxicity and provided similar levels of cytoreduction to conventional ALL protocols, without improving long-term outcomes.
ABSTRACT
We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph+) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCR-ABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph+ acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens. Cohort 2 had a complete response (CR) rate of 93% and 5-year survival of 69%. For newly diagnosed Ph+ ALL, survival was superior in cohort 2 compared with cohort 1. Toxicity was similar to that expected for chemotherapy alone. Among 10 evaluable patients, rapid loss of phospho-CRKL occurred during the imatinib window in seven patients (all achieved CR) and incomplete inhibition in three patients (none with CR). In summary, a pharmacodynamic window design permitted biomarker assessment of BCR-ABL targeting without compromising clinical outcomes.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Imatinib Mesylate/therapeutic use , Philadelphia Chromosome/drug effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adaptor Proteins, Signal Transducing/metabolism , Adolescent , Adult , Aged , Biomarkers, Tumor/blood , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use , Doxorubicin/therapeutic use , Female , Fusion Proteins, bcr-abl/metabolism , Humans , Male , Middle Aged , Nuclear Proteins/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Reverse Transcriptase Polymerase Chain Reaction , Verapamil/therapeutic use , Vincristine/therapeutic use , Young AdultABSTRACT
Adolescents and adults with acute lymphoblastic leukemia/lymphoma (ALL) have better outcomes when treated using pediatric protocols compared with treatment using adult protocols. We reviewed the progress and outcomes of 40 adolescents and adults up to 45 years of age, from three Australian centers, treated on the intensive French group for childhood ALL (FRALLE)-93 pediatric protocol. All except one patient achieved a morphologic complete remission following induction chemotherapy. Three-year overall survival for all-risk and standard-risk disease was 70% and 75%, respectively. The treatment protocol was generally well tolerated with no treatment related mortality. The FRALLE-93 pediatric protocol showed excellent overall survival for patients with standard-risk disease, without the need for allogeneic hematopoietic stem cell transplant in first remission.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Consolidation Chemotherapy , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Induction Chemotherapy , Maintenance Chemotherapy , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Risk Factors , Transplantation, Homologous , Treatment Outcome , Young AdultABSTRACT
Chronic myeloid leukemia (CML) management varies across Asia due to disparities in affluence and healthcare provision. We surveyed CML management practice at 33 hospitals in 14 countries/regions to identify treatment challenges and opportunities for harmonization. Patients were generally treated according to international guidelines; however, tyrosine kinase inhibitors (TKIs) and molecular monitoring are inaccessible to many patients not covered by national insurance or eligible for subsidized treatment. Late diagnosis and suboptimal monitoring, often due to cost and accessibility issues, are challenges. Priorities for Asia include: extending accessibility to TKIs; specialist laboratory monitoring; and enriching data to support regional CML management guidelines.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Asia , Data Collection , Delayed Diagnosis , Drug Delivery Systems , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/economics , Pacific Islands , Patient Care Management/economics , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitorsABSTRACT
We report the second case of Hb Titusville in a family of Northern European background. This variant hemoglobin caused by an alpha-globin gene mutation has decreased oxygen affinity. Correct diagnosis is clinically important to spare affected individuals extensive investigations into other causes of low oxygen saturation in peripheral blood.