Haploidentical bone marrow transplants for hematological malignancies using non-myeloablative conditioning therapy and post-transplant immunosuppression with cyclophosphamide: results from a single Australian centre

Background: HLA haploidentical bone marrow transplantation is a treatment option in patients with hematological malignancies who have no available HLA matched donor, but is limited by conditioning regimen toxicity, graft failure, relapse and graft versus host disease. Aims: To demonstrate safety and efficacy of haploidentical bone marrow transplantation with nonmyeloablative conditioning and high-dose post-transplant cyclophosphamide in adult patients with leukaemia or lymphoma. Methods: 12 patients, median age of 51 years, underwent transplantation with T cell replete bone marrow from a haplotype matched relative. The conditioning regimen consisted of cyclophosphamide, fludarabine, and low-dose TBI. Post-transplant immunosuppression consisted of a single dose of cyclophosphamide 50 mg/kg on day 3, followed by oral tacrolimus and mycophenolate mofetil. Outcomes reported are overall survival, engraftment and chimerism, toxicity, and clinical outcome. Results: All patients had neutrophil recovery (median 14.5 days), and 11 of 12 had platelet engraftment (median 17 days). Two patients had autologous reconstitution. Seven of 9 assessable patients had complete donor chimerism. Four patients had grade II-III GvHD, and none had grade IV GvHD. Four patientsdeveloped limited stage chronic GvHD. Five patients with AML relapsed. Two patients died of non-relapse causes, both from other malignancies, and 5 patients remain alive and relapse free. Median overall survival was 324 days (range 88-1163). Conclusion: This regimen is feasible and well-tolerated in older patients with high risk leukemia or lymphoma, with minimal short-term toxicity, and low rates of GVHD. The proportion of disease-free survivors indicates a graft versus malignancy effect is present in survivors. Keywords: hematological malignancy, bone marrow transplant, haploidentical, post-transplant cyclophosphamid

Haploidentical bone marrow transplants for hematological malignancies using non-myeloablative conditioning therapy and post-transplant immunosuppression with cyclophosphamide: results from a single Australian centre

Background: HLA haploidentical bone marrow transplantation is a treatment option in patients with hematological malignancies who have no available HLA matched donor, but is limited by conditioning regimen toxicity, graft failure, relapse and graft versus host disease. Aims: To demonstrate safety and efficacy of haploidentical bone marrow transplantation with nonmyeloablative conditioning and high-dose post-transplant cyclophosphamide in adult patients with leukaemia or lymphoma. Methods: 12 patients, median age of 51 years, underwent transplantation with T cell replete bone marrow from a haplotype matched relative. The conditioning regimen consisted of cyclophosphamide, fludarabine, and low-dose TBI. Post-transplant immunosuppression consisted of a single dose of cyclophosphamide 50 mg/kg on day 3, followed by oral tacrolimus and mycophenolate mofetil. Outcomes reported are overall survival, engraftment and chimerism, toxicity, and clinical outcome. Results: All patients had neutrophil recovery (median 14.5 days), and 11 of 12 had platelet engraftment (median 17 days). Two patients had autologous reconstitution. Seven of 9 assessable patients had complete donor chimerism. Four patients had grade II-III GvHD, and none had grade IV GvHD. Four patientsdeveloped limited stage chronic GvHD. Five patients with AML relapsed. Two patients died of non-relapse causes, both from other malignancies, and 5 patients remain alive and relapse free. Median overall survival was 324 days (range 88-1163). Conclusion: This regimen is feasible and well-tolerated in older patients with high risk leukemia or lymphoma, with minimal short-term toxicity, and low rates of GVHD. The proportion of disease-free survivors indicates a graft versus malignancy effect is present in survivors. Keywords: hematological malignancy, bone marrow transplant, haploidentical, post-transplant cyclophosphamid

Real‐world experience: Introduction of T cell replete haploidentical transplantations in a single center

OBJECTIVES: The aim of this study was to describe real‐world data on outcomes of T cell replete haploidentical hematopoietic stem cell transplantation (HSCT) after the introduction of this modality in a single center and to compare them with different donor types. METHOD: Outcomes of 30 consecutive patients with hematological malignancies that received T cell replete haploidentical HSCT with posttransplantation cyclophosphamide (PTCY) from 2016 to 2018 in our center were analyzed and compared to the outcome of human leukocyte antigen (HLA)‐related and unrelated matched donor HSCT (n = 97) and to a historical cohort of T cell depleted haploidentical HSCT (n = 11). RESULTS: One year graft‐versus‐host‐free, relapse‐free survival in haploidentical HSCT was comparable with other donor types (haplo 40%, matched related donor [MRD] 33%, matched unrelated donor [MUD] 25%, p = 0.55). Non relapse mortality was high in haploidentical HSCT (50%), mostly due to infectious complications. However, relapse rates were only 3%, and OS and progression‐free survival after 1 year were 47% and thereby also similar to HLA‐matched HSCT in our center (MRD 53%, MUD 48%). CONCLUSION: Our data show that T cell replete haploidentical HSCT has similar outcomes to HLA identical HSCT after introduction in our center. More strict adaptation on infection prevention was a crucial aspect of our learning curve. Overall, this type of transplantation is a feasible option when lacking an HLA‐identical donor. This option has advantages over an unrelated donor as it brings less logistical challenges than MUD transplantations

Second cancer risk in adults receiving autologous haematopoietic SCT for cancer: A population-based cohort study

Population-based evidence on second cancer risk following autologous haematopoietic SCT (HCT) is lacking. We quantified second cancer risk for a national, population-based cohort of adult Australians receiving autologous HCT for cancer and notified to the Australasian Bone Marrow Transplant Recipient Registry 1992-2007 (n=7765). Cancer diagnoses and deaths were ascertained by linkage with the Australian Cancer Database and National Death Index. Standardized incidence ratios (SIRs) were calculated and Cox regression models were used to estimate within-cohort risk factors treating death as a competing risk. During a median 2.5 years follow-up, second cancer risk was modestly increased compared with the general population (SIR 1.4, 95% confidence interval 1.2-1.6); significantly elevated risk was also observed for AML/myelodysplastic syndrome (SIR=20.6), melanoma (SIR=2.6) and non-Hodgkin lymphoma (SIR=3.3). Recipients at elevated risk of any second cancer included males, and those transplanted at a younger age, in an earlier HCT era, or for lymphoma or testicular cancer. Male sex, older age (>45 years) and history of relapse after HCT predicted melanoma risk. Transplantation for Hodgkin lymphoma and older age were associated with lung cancer risk. Second malignancies are an important late effect and these results inform and emphasize the need for cancer surveillance in autologous HCT survivors. © 2014 Macmillan Publishers Limited

The role of stem cell transplantation in the management of relapsed follicular lymphoma in the era of targeted therapies

Patients with relapsed follicular lymphoma (FL) following first-line therapy have an increasing number of management strategies ranging from observation through to stem cell transplantation. There has been an exciting expansion in novel agents to treat FL, but at present there is not a universally accepted standard of care in the relapse setting. Decision-making can be difficult for the clinician as there is a paucity of data to compare the various relapse therapies available. This review will discuss conventional therapy for relapsed FL, consider the use of novel agents and explore the role and timing of autologous and allogeneic stem cell transplantation

Secondary solid cancer screening following hematopoietic cell transplantation

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients