Journal of Clinical and Experimental Transplantation
Open Access

Relapse acute; Leukemia; Second transplant

Introduction

Children with acute myelogenous leukaemia (AML) or acute lymphoblastic leukaemia (ALL) who relapse after their initial allogeneic hematopoietic cell transplant have few treatment choices (HCT). Although a second HCT is a possibility, its outcome depends on the first HCT’s performance status, the time between the first HCT and recurrence, the disease condition at the second HCT, and the morbidities from the first and salvage chemotherapies [1]. Prior studies have only minimally included children and have primarily concentrated on adults with acute and chronic leukaemia. Of the 2632 second HCT patients in the largest study, 569 (21%) were children and adolescents. This study found that a diagnosis of chronic myeloid leukaemia, a longer period of time in remission following the first HCT, and a longer gap between HCTs improved survival after the second procedure. Both the first and second HCTs, the second HCT’s low disease burden, the patient’s youth, the absence of any prior acute or chronic graft-versus-host disease (GVHD), and the transplantation period’s most recent duration [2]. The study came to the conclusion that switching the donor for the second HCT was not beneficial. The three prior studies with kids came to the same conclusion: low disease load, length of remission after first HCT, and time between first and second HCT are all significant predictors of survival [3].

Methods

Over 400 transplantation sites that participate voluntarily in the CIBMTR submit data prospectively on subsequent transplantations. Till death or loss to follow-up, patients are longitudinally followed [4]. Patients with AML or ALL who underwent a second HCT for relapse (morphologic, cytogenetic, or molecular) after their first allogeneic HCT are included in the current analyses if they are less than 25 years old. Patients who underwent myeloablative (1000 cGy total body dosage, 10 mg/kg busulfan, >140 mg/m2 melphalan) and reducedintensity conditioning regimens were included. Between 2001 and 2014, every second HCT was carried out. Written informed consent for the study was given by parents or patients who were at least 18 years old. This research was approved by the National Marrow Donor Program’s Institutional Review Board [5].

LFS, or the likelihood of being in remission and surviving, served as the main goal. Death from any cause or relapse was both regarded as events (treatment failure). The possibility of being alive was referred to as overall survival (OS) [6-8]. Any death was regarded as an event, and at the last follow-up, patients who were still alive were censored. The goal of neutrophil recovery was to maintain an absolute neutrophil count for three days in a row and a platelet count of 20 109/L for seven days without transfusion therapy. Using established criteria, records from each transplantation facility were used to determine the severity of Grade II–IV acute GVHD and chronic GVHD. Leukemia morphologic, cytogenetic, or molecular recurrences were all considered relapses. Death in remission was referred to as nonrelapse mortality [9].

Result

The study population’s traits are displayed. The study population’s median age at second HCT was 11, and 21% of them were young adults (18 to 24 years). 75 percent of patients were in hematologic remission at transplantation, and 72 percent of patients achieved performance scores of 90 or 100. One-third of the patients had their second HCT less than a year after their first HCT [10], with the median interval between their first and second HCTs being 17 months. Only 14% of the patients had both transplants performed using the same donor, whereas 92% of patients obtained their graft from an unrelated donor. Twelve donors were HLA-matched siblings, thirteen were HLA-matched friends, and 36 patients received grants from the same donor for both transplants [11].

Discussion

There are numerous published reports on second HCT results, primarily focusing on adults. Age, the time between the first HCT and recurrence and the disease condition prior to transplantation have all been repeatedly recognised as predictive for survival factors. Our study population, which has a median age of 11 years and describes outcomes following second HCT in a relatively young cohort of AML or ALL patients who relapsed after undergoing the first HCT The disease status at second HCT was linked with recurrence, LFS, and OS, consistent with all other data, including a recent European research [12], suggesting that cautious patient selection for second HCT can extend LFS and OS. In the first year following HCT, nonrelapse mortality was high, ranging from 20% to 30%. From year 1 to year 8 after HCT, only a small number of incidents with a 5% absolute increment followed. The most common reason for second HCT failure was recurrent leukaemia, but the recurrence pattern varied according on the severity of the disease. The majority of incidents for individuals who underwent HCT in relapse happened within the first year after HCT. Patients who underwent HCT when in remission experienced relapse over a longer period of time, which led to a 10% decline in LFS after the first year following HCT. These facts are both instructive and difficult. First and foremost, as the burden of illness is crucial for a successful outcome, thorough patient selection for second HCT is essential. The transplantations in this study took place over a period of 15 years, and the recommendations for moving forward to transplantation have changed throughout time.

Conclusion

The totality of research demonstrating the detrimental impact of minimum residual disease (MRD) on ALL relapse and survival makes it compelling to propose that second HCT should be made available for patients who cannot have MRD diagnosed. Additionally, there is mounting proof that the identification of leukaemia at subclinical stages in AML by molecular-based or multipara meter flow cytometry is also independently prognostic prior to HCT. Second, given the growing number of novel agents available for the treatment of ALL and AML, our findings highlight the importance of carefully choosing patients who can tolerate continued treatment after HCT. The goal of planned therapy is to achieve MRD negativity to reduce the risk of relapse after second HCT. Others have discussed the significance of the length of remission following the initial HCT as a predictive factor for survival.

Instead, we found that LFS was improved throughout the time between relapse and second HCT. In this study, the demonstrated benefit for LFS in the timing of second HCT serves as a proxy for the length of remission following first HCT. One-half of patients who underwent second HCT 6 months after relapse had a remission lasting longer than 12 months between their first HCT and their post-HCT relapse. In contrast, for 56% of patients receiving second HCT 6 months after recurrence, the time between the initial HCT and subsequent relapse was less than 12 months.

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