First-line high-dose therapy and autologous blood stem cell transplantation in patients with primary central nervous system non-Hodgkin lymphomas—a single-centre experience in 61 patients

Primary central nervous system non-Hodgkin lymphomas (PCNS-NHLs) are extranodal B-cell lymphomas with poor prognosis. The role of high-dose therapy (HDT) followed by autologous blood stem cell transplantation (ASCT) as first-line therapy is still not clear. We retrospectively collected long-term follow up data of 61 consecutive patients with PCNS-NHL at the University Hospital Düsseldorf from January 2004 to December 2016. Thirty-six patients were treated with conventional chemoimmunotherapy (cCIT) only (CT-group). Seventeen patients received an induction cCIT followed by HDT and ASCT. In the CT-group, the overall response rate (ORR) was 61% (CR 47%, PR 14%), and there were 8% treatment-related deaths (TRD). Progression-free survival (PFS) was 31.8 months, and overall survival (OS) was 57.3 months. In the HDT-group, the ORR was 88% (59% CR, 29% PR), and there were 6% TRD. Median PFS and OS were not reached at 5 years. The 5-year PFS and OS were 64.7%. After a median follow up of 71 months, 10 patients (59%) were still alive in CR/PR following HDT and ASCT, one patient was treated for progressive disease (PD), and 7 had died (41%, 6 PD, 1 TRD). All patients achieving CR prior to HDT achieved durable CR. In the CT-group, 8 patients (22%) were alive in CR/PR after a median follow-up of 100 months. Twenty-eight patients died (78%, 24 PD, 2 TRD, 2 deaths in remission). In the univariate analysis, the HDT-group patients had significantly better PFS (not reached vs 31.8 months, p = 0.004) and OS (not reached vs 57.3 months, p = 0.021). The multivariate analysis showed HDT was not predictive for survival. Treatment with HDT + ASCT is feasible and offers the chance for long-term survival with low treatment-related mortality in younger patients. In this analysis, ORR, PFS and OS were better with HDT than with conventional cCIT alone. This result was not confirmed in the multivariate analysis, and further studies need to be done to examine the role of HDT in PCNSL.

Haploidentical Peripheral Blood Stem Cell Transplantation (Haplo-PBSCT) with Cyclophosphamide Pos Transplant (CyPost) in High-Risk Hematologic Malignancies. Results of 5 Years in Transplant Center in Northeast of Mexico

Introduction: Haploidentical peripheral blood stem cell transplantation ( Haplo-PBSCT) is a curative option in patient with hematology malignancy. In Mexico is very difficult to find an identical HLA donor , for this reason Haplo PBSCT it is an option in our public Health institution. Materials and methods: we aimed a retrospective study since (2017 -2021) in our Hospital Unidad Médica de alta Especialidad 25, Instituto Mexicano del Seguro Social (IMSS UMAE 25) Monterrey, Mexico. We include patients over 15 years of age who were undergo Haplo PBSCT with hematolgy malignancies . We performed Analysis of Overall and Relapse-free survival with kaplan meier curves and incidence of acute and chronic graft versus host disease (GVHD) and percentage of Transplant-Related Mortality (TRM). Results: we analized a 38 patients, the median age was 35 years (range 15-64). Of the total , 25 were male (65%) and 13 famale (34%). The rest of baseline data is described in table 1. The median time of neutrophil engrafment was days 17 ( 11-26 ) and platelets was 19.5 days ( 12-38 ). The Incidence of Primary Graft failure was 18 % ( seven patients). Patients with graft had 99-100% chimerism at day 100. The Incidence of aGVHD was 26 % and the cGVHD was 16%. DLI was used in four patients to treat passenger lymphocyte syndrome (2 patients) and ( 2 patients) with severe graft rejection. The principal cause of death was sepsis in eleven patients (29%). Two patients with acute leukemia (AML and ALL) died after development of post transplant lymphoproliferative disease. The TRM was 28.2%. There were no relapse-related deaths during follow-up after Haplo-PBSCT. The median of survival was 4.5 months ( range 1-44) with Overall Survival (OS) of 42 % at 3 years ( figure 1). Conclusion: Our analysis shows results that were comparable with those published in first world international transplant centers . Relapse remains the major cause of transplant failure, in our population the antigenic disparity between donor and recipient can strengthen the immune response versus disease. Haplo-PBSCT is a feasible transplantation method in patients with hematological malignancies in developing countries with limited resources. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Unmanipulated Peripheral Blood Stem Cell Transplantation with non-TBI Myeloablative Conditioning Regimen from Haploidentical and Unrelated versus Related Donors for Acute Leukemia in Children, Adolescents and Young Adults (CAYA): A Competing Risk Analysis

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for acute leukemia. Many different parameters have significant impact on the final results of HSCT such as donor type, stem cell source, and the implemented conditioning regimen. In the absence of an HLA-matched related donor, unrelated donors or haploidentical donors are possible alternatives for patients with an indication to HSCT. In order to compare the outcomes of HSCT from different donor types, in this single-center study, using a radiation-free MAC regimen, we compared the results of unmanipulated peripheral blood stem cell transplantation (PBSCT) from matched and mismatched related and unrelated donors with haploidentical donors in the children, adolescents and young adults (CAYA) affected by acute leukemia.MethodsIn this retrospective study, since 2014 to 2021, the outcome of CAYA patients with acute leukemia who had undergone peripheral blood T cell-replete HSCT from haploidentical donors versus unrelated donors (including 10/10 or 9/10 HLA-matched) versus related donors (including 10/10 or 9/10 HLA-matched) were evaluated. The HSCT was based on a radiation-free MAC regimen including Busulfan and Cyclophosphamide. The GvHD prophylaxis was based on the administration of Cyclosporine A in all patients, plus rabbit anti-human thymocytes globulins in unrelated and haploidentical donors and post transplantation cyclophosphamide in haploidentical donors. Adjusted multivariable proportional hazard Cox and competing risk analyses were performed.ResultsMedian follow up time was 28.7 months (95% CI: 21.9-34.9). Three-year overall survival rate (OS) and GvHD-free/relapse-free survival (GFRFS) rate was 68.81% (95% CI: 60.08%-76.01%) and 44.19% (95% CI: 35.52%-52.49%), respectively. Patients who had undergone HSCT from an unrelated donor had the lowest OS and GFRFS compared to other donor types. The 3-years NRM in all patients was 7.84% (95% CI 4.36-12.62). Adjusted multivariable modeling of OS showed that the hazard of death in patients who had undergone HSCT from an unrelated donor, was 3.6 times more than patients who underwent HSCT from their haploidentical donors (P=0.05). Likewise, the hazard of NRM after HSCT from unrelated donors was 6 times more than haploidentical donors (P=0.002). However, the relapse incidence was not significantly different between the two mentioned groups.ConclusionsIn this study, HSCT from haploidentical donors was associated with superior survival rates compared to HSCT from unrelated donors. So haploidentical peripheral blood derived HSCT could be a practical and valuable clinical option that offers CAYA patients with acute leukemia needing HSCT and lacking matched available donors, a reasonable opportunity for disease control.

Two Cases of Tacrolimus-related Transplant-associated Thrombotic Microangiopathy Retinopathy after Allogenic Peripheral Blood Stem Cell Transplantation

Purpose: We report two cases of tacrolimus-related transplant-associated thrombotic microangiopathy (TA-TMA) retinopathy in leukemia patients who had undergone allogenic peripheral blood stem cell transplantation (PBSCT).Case summary: (Case 1) A 58-year-old woman with a history of PBSCT due to acute myelocytic leukemia and taking tacrolimus was referred to the ophthalmology clinic with visual disturbance. Her visual acuity (VA) was 0.4 in the right eye and 0.5 in the left eye. Multiple cotton wool spots and retinal hemorrhages were found in both eyes on fundus examination. Multiple capillary non-perfusions were seen on fluorescein angiography (FA). Tacrolimus-related TA-TMA retinopathy was suspected. Tacrolimus was discontinued and plasmapheresis was performed. After 3 months, neovascular glaucoma developed and her VA became “counting fingers” at 20 cm in both eyes. (Case 2) A 20-year-old man with a history of PBSCT due to acute lymphocytic leukemia and taking tacrolimus was referred to our clinic because of decreased VA in both eyes. His VA was 0.05 in the right eye and 0.025 in the left eye. Fundus and FA findings were the same as in Case 1, and the patient was suspected to have tacrolimus-related TA-TMA retinopathy. Tacrolimus was discontinued and plasmapheresis was performed. His VA was 0.2 in the right eye and 0.4 in the left eye at 1 month after treatment.Conclusions: It is necessary to consider TA-TMA retinopathy in leukemia patients taking calcineurin inhibitors, such as tacrolimus, who have decreased VA. Early diagnosis and treatment are important.