Minimal residual disease in Acute Lymphoblastic Leukemia in the context of hematopoetic stem cell transplantation

Minimal or measurable residual disease (MRD) is considered the most important independent prognostic factor in acute lymphoblastic leukemia (ALL). MRD status after clinical remission has been used to establish the risk of relapse and therapeutic stratification, identifying patients who can benefit from therapeutic intensification, including allogeneic stem cell transplantation (alloSCT). The pre alloSCT MRD also identifies patients eligible for transplant and those with low or high risk of relapse after transplantation, according to the level of MRD detected. However, MRD status post-alloSCT has been shown to be a more powerful predictor of relapse than pre-transplant MRD. In addition, it is important to take into account that there are some factors to be considered to better interpret MRD information, these include: the method used for MRD assessment and its sensitivity and specificity, which may vary according to each specific time point of evaluation; the treatment regimen used; and the identification of genetic lesions that combined with MRD information can further improve the management of patients with ALL.

Resiliency, the Lived Experience of Patients Undergoing Hematopoietic Stem Cell Transplantation

Background: Hematopoetic stem cell transplantation is considered as a standard treatment for cancer patients to stay hopeful toward treatment outcome. However, these patients experience many complications which might affect different aspects of their life. The aim of this study was to investigate the lived experience of patients after hematopoetic stem cell transplantation and introduce supportive care strategies. Materials and Methods: In this study, Van Manen’s Hermeneutic phenomenological approach was used. Eleven patients (7 males and 4 females) were chosen by targeted sampling from visitors of Shariati Hospital’s outpatient clinic. Semi-structured interviews were conducted and the final data were analyzed by MAXQDA 10 software. Results: Data analysis revealed that the main theme was resiliency with two sub-themes of “not surrendering to disease” and “feeling closer to God”. Conclusion: Participants declared that transplantation was like a second chance for life and considered this opportunity as a gift from God to overcome their disease. According to our findings, spirituality aids can help patients control the disturbances following HSCT and health professionals can use constructive strategies to support patients with spiritual needs.

Is the End Close for the Graft-Versus-Host Disease That Is a Big Problem Following Allogeneic Hematopoetic Stem Cell Transplantation?

Introduction:Despite major improvements in allogeneic hematopoetic stem cell transplantation (Allo-SCT) form matched related/unrelated donor over last decades, chronic graft-versus-host disease (cGVHD) is still the leading cause of late treatment-related deaths among recipients (Lee et all, Blood2002). Novel insights into the pathophysiology of GVHD highlighted the relevant role of the host inflammatory response governed by Bruton tyrosine kinase (BTK) signaling pathway. Ibrutinib is a first class, once daily inhibitor of BTK with proven efficacy in B cell lympho-proliferative diseases, was recently employed in corticosteroid- refractory chronic GVHD with encouraging overall response rates(Miklos et all, Blood 2017). Patients and Methods:This real-life, multicenter retrospective study conducted in 6 centers from Turkey included 14 adult patients diagnosed with steroid-refractory cGVHD. All patients were transplanted using grafts from HLA-matched peripheral blood stem cell source. We treated off-label these patients from June 2017 to July 2018 with ibrutinib with a dose of 420 mg P.O. qday. Organ sites affected and cGVHD grading before starting ibrutinib were classified according to the National Institues of Health (NIH) 2014 criteria. Steroid refractory cGVHD was defined as any disease that failed to respond to previous immunosuppressive therapy with steroids at least 4 weeks or inability to taper it with or without additional immunosuppressive drugs. Results:The baseline characteristics of the patients are listed in Table 1. Patients had undergone both myeloablative and non-myeloablative Allo-SCT for a variety of underlying hematological malignancies. As expected mouth and skin were the most frequently involved organs and 79% of patients showed evidence of cGVHD in more than 2 organs. The median Karnofsky Performance Status score was 75% (30%-100%). At a median follow-up of 26.7 months (range, 3.2-70.9 months) after evidence of cGVHD showed, 12 (85.7%) patients were still receiving ibrutinib and 2 (14.3%) had discontinued treatment, because of cGVHD progression. Treatment duration ranged from 2 to 12 months (median 6 months) for all patients. Only one patient had grade 2 muscle spasms as adverse event and need to reduce the 25% of drug dosage. No several adverse events due to ibrutinib was observed in our cohort. In the all treated population, the overall response rate (ORR), based on the 2005 NIH cGVHD Consensus Panel response criteria, was 71.4%, with a CR rate of 28.6 % and a PR rate of 42.9 %. For the responders, the median time to initial response was 28 days. Two patients had stable disease under the ibrutinib treatment and still continue receiving. Analysis by organ domain showed similar rates of response in the skin (91.7%), lung (85.7%) and mouth (80%). However the response in the liver (71.4%) was lower than the others. At the time of data collection, no patient has deceased. Discussion:In the absence of an approval treatment of steroid-refractory cGVHD, there is currently no consensus on the optimal second-line treatment. Treatment choices are based on mostly physician experience, ease of use and risk of toxicity. Based on the results of our limited study; the clinically meaningful response with safety profile observed with ibrutinib as a salvage therapy for chronic GVHD in accordance with Miklos and colleagues's report. However, in contrast to their results; patients with skin and lung manifestations of cGVHD were appeared to have somewhat better responses to ibrutinib than patients with cGVHD involving liver. It is important to note that prospective randomized controlled studies with large number of patients are warranted to find out the standard regimen for steroid-refractory cGVHD. Disclosures Ilhan: Alexion: Speakers Bureau; Roche: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau. Civriz Bozdag:TAKEDA: Consultancy; MSD: Research Funding; NOVARTIS: Consultancy. Özcan:Takeda: Honoraria, Other: Travel payment, Research Funding; Novartis: Research Funding; Roche: Honoraria, Research Funding; Abbvie: Other: Travel payment; Jazz: Other; Janssen: Other: Travel Support, Research Funding; BMS: Honoraria; Bayer: Research Funding; MSD: Research Funding; Celgene: Other: Travel support, Research Funding; Archigen: Research Funding; MSD: Other: travel support, Research Funding; Jazz: Other: Travel support.