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Staging System to Predict the Risk of Relapse in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

ABSTRACT: Over the last decade autologous stem cell transplantation (ASCT) has emerged as the standard of care in the management of Multiple Myeloma (MM). However, the cases of early relapse (within 36 months) after the stem cell rescue remains a significant challenge. For a lot of practical purposes, it is crucial to identify whether a patient undergoing ASCT falls into the high-risk group (likely to relapse within 36 months) or a low risk one. Our analysis showed that existing MM staging systems (International Staging System or ISS and Durie Salmon Staging or DSS) are not sufficient to discriminate between the risk groups significantly. To address this, we gathered a total of 39 clinical and laboratory parameters of 347 patients from the Department of Medical Oncology of All India Institute of Medical Sciences (AIIMS). We employed a stacked machine learning model consisting spectral clustering and Fast and Frugal Tree (FFT) technique to come up with a 3-factor multivariate 2-stage staging scheme, which turns out to be extremely decisive about the outcome of the stem cell rescue. Our model comes up with a three-factor (1. if patients has relapsed following remission, 2. response to induction, 3. pre-transplant Glomerular Filtration Rate or GFR) staging scheme. The resulting model stratifies patients into high-risk and low-risk groups with markedly distinct progression-free (median survival-24 months vs. 91 months) and overall survival (median survival-51 months vs. 135 months) patterns.

SUBMITTER: Goswami C

PROVIDER: S-EPMC6640159 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Staging System to Predict the Risk of Relapse in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

Goswami Chitrita C Poonia Sarita S Kumar Lalit L Sengupta Debarka D

Frontiers in oncology 20190712

Over the last decade autologous stem cell transplantation (ASCT) has emerged as the standard of care in the management of Multiple Myeloma (MM). However, the cases of early relapse (within 36 months) after the stem cell rescue remains a significant challenge. For a lot of practical purposes, it is crucial to identify whether a patient undergoing ASCT falls into the high-risk group (likely to relapse within 36 months) or a low risk one. Our analysis showed that existing MM staging systems (Intern ...[more]

PMID: 31355145

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Project description:IntroductionMultiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur. Nevertheless, some patients achieve sustained responses after successful induction treatment and ASCT.MethodsWe retrospectively evaluated all patients diagnosed with MM in our institution who underwent induction treatment and ASCT between 1990 and 2015. The subset of patients who achieved a sustained response (any degree) for 5 or more years after ASCT without further treatment or signs of progression were distinguished as "long-term responders" (LTRs). In the non-LTR group, a cohort referred to as "prolonged responders" (PLRs) showed sustained response of at least 5 years after ASCT but eventually relapsed. We collected and analyzed clinical and laboratory data.ResultsTwo hundred and fifty patients were diagnosed with MM and received induction treatment and ASCT at our institution in the study period. Among them, 54 (21.6%) patients met the criteria for LTR. Some diagnostic features such as a younger age, female gender, ECOG performance status of 0, lower International Staging System (ISS) stage, lower bone marrow plasma cell infiltration, and lower serum levels of calcium, C-reactive protein, and lactate dehydrogenase (LDH) were found to be more prevalent in LTR. Female gender, an ECOG performance status of 0, a localized Durie-Salmon stage, an ISS of I-II, the absence of bone disease, and an LDH within normal range were also predictive of longer progression-free survival (PFS) and overall survival (OS) in the whole cohort. The depth of the response achieved after induction and ASCT as well as the administration of an IMID-based maintenance regimen may play a role in the differences observed on PFS between cohorts. A detectable M-protein with a monoclonal gammopathy of undetermined significance (MGUS)-like behavior was detected in one-third of LTR after ASCT. Although relapses continue to occur in patients who achieve a 5-year treatment-free period after ASCT, a plateau is observed in the survival curves at approximately 21 years of follow-up.

Project description:Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient stem cells in case there is a need for stem cell boost for delayed/poor engraftment or for future second ASCT. However, collecting and storing backup stem cells in all patients requires significant resources and cost, and the rates of backup stem cell utilization are not well studied. We sought to examine the utilization of backup stem cells (BSCs) in patients with MM undergoing ASCT. Patients with MM aged ≥18 years old who underwent first ASCT at our institution from January 2010 through December 2015 and collected sufficient stem cells for at least 2 transplants were included in this single-center retrospective study. This timeframe was selected to allow for adequate follow-up. A total of 393 patients were included. The median age was 58 years (range, 25-73). After a median follow-up of 6 years, the median progression-free survival (PFS) of the cohort was 3 years. Sixty-one percent (n = 240) of patients progressed or relapsed. Chemotherapy-based mobilization was used in almost all patients (98%). The median total CD34+ cells collected was 18.2 × 106/kg (range, 3.4-112.4). A median of 5.7 × 106 CD34+ cells/kg (range, 1.8-41.9) was infused during the first ASCT, and a median of 10.1 × 106 CD34+ cells/kg (range, 1.5-104.5) was cryopreserved for future use. Of the patients, 6.9% (n = 27) used backup stem cells, with 2.3% (n = 10) using them for stem cell boost, 4.6% (n = 18) for a second salvage ASCT, including 1 patient for both stem cell boost and second ASCT. Rates of backup stem cell use among patients aged <60, 60-69, and ≥70 years were 7.8%, 5.7%, and 5.9%, respectively. There was a trend toward higher rates of backup stem cell use for second ASCT in patients who were younger, had suboptimal disease control at time of first ASCT, and longer PFS. The median dose of stem cell boost given was 5.6 × 106 CD34+ cells/kg (range, 1.9-20). The median time from stem cell boost to neutrophil, hemoglobin, and platelet engraftment was 4 (range, 2-11), 15 (range, 4-34), and 12 (range, 0-34) days, respectively. Lower CD34+ dose and older age at time of ASCT predicted need for stem cell boost. With new salvage therapies for relapsed MM, the rates of second ASCT are very low. The low rates of use suggest that institutional policies regarding universal BSC collection and long-term storage should be reassessed and individualized. However, need for stem cell boost in 2.3% of patients may present a challenge to that.

Dataset Information

Staging System to Predict the Risk of Relapse in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

Publications

Staging System to Predict the Risk of Relapse in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

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