Autologous Stem Cell Transplantation In Patients Research Articles

Skin Disinfection with 2% Chlorine Gluconate-Adine in Autologous Peripheral Hematopoietic Stem Cell Transplantation Patients

Skin Disinfection with 2% Chlorine Gluconate-Adine in Autologous Peripheral Hematopoietic Stem Cell Transplantation Patients

Retrospective Analysis of Autologous Stem Cell Transplantation for AL Amyloidosis: A Study from the Multiple Myeloma Working Group of the Japan Society for Hematopoietic Cell Transplantation

Autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with light-chain (AL) amyloidosis, but little is known about it in Asian populations. To investigate the outcome of and prognostic factors for ASCT, we retrospectively analyzed ASCT cases registered to the Transplant Registry Unified Management Program between December 1999 and December 2015, with extra clinical information collected through a secondary survey. The primary endpoint was overall survival (OS). Hematologic response, organ response, and transplantation-related mortality were analyzed as secondary endpoints. The database search identified 330 patients (median age, 57 years; range, 31 to 74), and the secondary survey provided details for the 110 patients (33.3%) included in the study cohort. Fewer than 3 organs were involved in 56.4% of the patients, with cardiac involvement in 57.3%. Performance status (PS) was 0 to 1 in 83.6%. The conditioning melphalan dose was reduced in 54.6%. Overall hematologic response was a partial response or better in 77.6% of the patients and a complete response in 49.3%. The 5-year OS was 70.1%. A PS of 0 to 1 was associated with a significantly better prognosis in terms of OS. Although survival after ASCT for AL amyloidosis improved over time, poor PS and cardiac involvement had negative impacts on prognosis. The early mortality after ASCT was 6.4%. Poor PS and cardiac involvement led to high early mortality. A brain natriuretic peptide (BNP) level of 400 pg/mL was associated with worse OS. Our study has several limitations inherent to a retrospective analysis using a questionnaire. The depth of response and biomarker responses were significantly limited by the degree of missing data. Nonetheless, our data support the importance of careful patient selection for good outcomes of ASCT in patients with AL amyloidosis. In our cohort, poor PS and cardiac involvement had a negative impact on prognosis, and BNP level was a useful prognostic factor.

The Efficacy of Plerixafor Plus Recombinant Human Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients with Lymphoma and Plasma Cell Diseases

Objective: Plerixafor is a small-molecule inhibitor of CXCR4. This study evaluates the efficacy of plerixafor combined with recombinant human granulocytic colony stimulating factor(G-CSF), in mobilizing hematopoietic stem cells for autologous stem-cell transplantation (ASCT) in patients with lymphoma and plasma cell diseases.Methods: A retrospective analysis was performed on 41 patients with Plerixafor combined with G-CSF admitted to the Department of Hematology, Nanfang Hospital, Southern Medical University,China from July 2019 to February 2021. Mobilization protocol: all patients were given G-CSF 10μg/kg d1-4 and Plerixafor 20mg (all patients weighed less than 83kg) 11 hours before collection on day 5 (night of day 4).Results: The median age of 41 patients was 52 years (25-66 years), the median body weight was 57kg (41-80kg), and the male to female ratio was 1.16:1(22/19). The patients of plerixafor used in combination with G-CSF include Multiple Myeloma 75.6%(31/41), Diffuse Large B Cell Lymphoma was 9.8%(4/41), Peripheral T Cell Lymphoma (4.9%, 2/41), Angioimmunoblastic T Cell Lymphoma (2.4% ,1/41), Systemic light chain (AL) amyloidosis (2.4% ,1/41), POEMS syndrome (2.4%,1/41), and plasma cell leukemia (2.4%, 1/41). Above the patients got partial remission（PR） before mobilization. 17 patients got complete remission（CR）, 4 patients got very good PR(VGPR) and ten got PR. There were 5 lymphoma patients with CR and 2 with PR. The majority of patients, 25, received first-line chemotherapy. 11 patients received second-line chemotherapy, and five received third-line myeloma therapy or above. The median cycle of chemotherapy was 4 (range 4-41). Twenty-two patients with multiple myeloma received treatment with lenalidomide regimens. 26 of all (63.4%) had optimum mobilization (CD34 positive cell count ≥5 × 10 6 cells/kg), and 36 (87.8%) had minimum mobilization (CD34 positive cell count ≥2 × 10 6 cells/kg). The minimum and optimum mobilization rate of first-line chemotherapy regimen was 92% and 72% respectively. The rate of the minimum mobilization of the second line chemotherapy was 100%, the optimum mobilization rate was 63.6%. The minimum and the optimum mobilization rate were 60% and 20% for the third line chemotherapy and above. The minimum mobilization rate was 94.7% and the optimum mobilization rate was 57.9% in patients receiving lenalidomide containing chemotherapy less than the 4 cycles. The minimum and optimum mobilization rate were 66.7% and 66.7% for patients with more than 4 cycles of lenalidomide chemotherapy. Thirty-four patients received autologous hematopoietic stem cell transplantation. Conditioning regimens was TBI (total-body irradiation) + CY (CTX)+ VP-16 or BUCY+ Me-CCNU protocol in lymphoma patients, and Melphala 200mg/m 2 in Multiple myeloma patients. A reduction of melphalan dose(140mg/m 2) in patients with severe renal failure, here defined as iohexol clerarance <30 ml/min, is suggested. Neutrophil engraftment was defined as neutrophil count ≥ 0.5 × 10 9/L for 3 days or ≥ 1.0 × 10 9/L for 1 day. Platelet engraftment was defined as platelet count ≥ 20 × 10 9/L without a transfusion from the preceding 7 days. All patients who received transplantation had successful neutrophil engraftment and 94.1% had successful platelet engraftment. The median time to engraftment was 10 days(9-13 days) for neutrophil and 11 days (9-48 days) for platelet. Using all available laboratory measurements and clinical information to determine graft failures, there were two platelet graft failures in at 1 month follow-up visit. However they had successful platelet engraftment after treatment with Eltrombopag or Avatrombopag(43 days, 48 days).Conclusions: The mobilized cells after G-CSF plus Plerixafor contained high numbers of hematopoietic stem cells, and engrafted very efficiently. G-CSF plus Plerixafor may be preferred for ASCT in patients with lymphoma and plasma cell diseases. DisclosuresNo relevant conflicts of interest to declare.

Is There a Higher Incidence of Graft Failure or Delayed Time to Engraftment in Patients Undergoing Autologous Stem Cell Transplantation Who Receive Olanzapine for Anti-Emetic Prophylaxis?

Olanzapine has been shown to significantly decrease nausea and emetic episodes associated with chemotherapy in patients undergoing hematopoietic stem cell transplant (Monson, Greer, Kreikemeier, & Liewer, 2020). Additionally, Olanzapine has been shown to improve clinical outcomes in autologous stem cell transplant patients when added to triplet anti-emetic therapy of ondansetron, fosaprepitant and dexamethasone without any negative effects on time to engraftment (Clemmons, et al., 2018). Although this study did not show any delay in time to engraftment, there is only a small amount of data looking at this question, including Clemmons et al. (2016) and Trifilio et al. (2017). Other studies (Navari et al., 2016) demonstrated a decrease in chemotherapy related nausea and vomiting in patients receiving Olanzapine, but did not provide data on engraftment times as this was in standard chemotherapy recipients.At Colorado Blood Cancer Institute (CBCI), Olanzapine was used for a period of time for anti-emetic prophylaxis both pre and post autologous stem cell transplant. There was concern regarding whether or not Olanzapine was causing delays in time to engraftment or even potentially graft failure and use of the drug in transplant anti-emetic regimens was discontinued.We hypothesized that Olanzapine does not cause higher incidence of graft failure, as compared to patients who do not receive Olanzapine as part of their anti-emetic regimen during the pre and post autologous stem cell transplant period. A retrospective analysis (n = 272) was conducted on patients who underwent autologous stem cell transplant between 2019 and 2020. 134 of these patients received Olanzapine during conditioning and up until time of engraftment, and 138 patients had no Olanzapine exposure throughout their conditioning and transplant. Conditioning regimens were equal between the two groups (Table 1). The average number of days on Olanzapine was 10.7, and the average dose was 7.5mg daily. For the purposes of this study engraftment was defined as the first day post stem cell infusion that the patient had an absolute neutrophil count (ANC) of greater than or equal to 500.Findings showed that the mean day of engraftment in the patients with Olanzapine exposure was 14.69; in the non-Olanzapine group, the mean day of engraftment was 12.64 (Table 2). Using the two-sample t-test, this difference (2.05 days, 95% CI (1.60-2.51)) is significant (p<.0001).Based on our findings, there is evidence to support Olanzapine causing a slightly delayed time to engraftment in autologous stem cell transplant patients, but not a higher incidence of graft failure, although a randomized controlled trial would be needed to fully investigate. There is clear data showing increased ability to manage chemo therapy induced nausea and vomiting. While a randomized controlled trial would be needed to fully investigate, given there is not a proven increase in graft failure, Olanzapine should be considered as a desirable option to treat and prevent chemotherapy induced nausea and vomiting in autologous stem cell transplant patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Olanzapine (Zyprexa) - Used off-label for the treatment and prevention of chemotherapy induced nausea and vomiting

Clonal Hematopoiesis Prevalence Increases throughout Treatment of Newly Diagnosed Multiple Myeloma Patients

Clonal Hematopoiesis Prevalence Increases throughout Treatment of Newly Diagnosed Multiple Myeloma Patients

Outcomes of Single Versus Tandem Hematopoietic Stem Cell Autologous Transplant in High-Risk Myeloma Patients: A Single-Center Experience

Introduction: Over the past decade, significant advances in the treatment strategy of newly diagnosed multiple myeloma patients (NDMM) have challenged the initial management strategy in transplant-eligible (TE) patients. The value of a single autologous stem cell transplant (ASCT) is established in standard-risk myeloma; however, the role for tandem ASCT reveals conflicting results, especially in patients with high-risk cytogenetic (HR) features. HR changes include at least one of the cytogenetic lesions: t(4;14), t(14;16), t(14;20), del17p, 1q amp +, 1q amp + del 1p. Subgroup analyses of HR patients in the EMN02 study suggest benefits with tandem ASCT.Methods: We retrospectively reviewed our single centre ASCT experience in TE NDMM patients with HR from London, Canada, from January 1, 2007, to April 30, 2021 with the primary objective to compare single versus tandem ASCT for patients with high-risk MM. Secondary objectives include progression-free survival (PFS), overall survival (OS) and the effect of maintenance therapy on survival. OS and PFS were estimated using the Kaplan-Meier method. We also applied univariate and multivariate cox regression to assess the effects of age, hemoglobin, and creatinine on survival.Results: 155 NDMM received at least one ASCT between January 1, 2007 to April 30, 2021. 61/155 (39.3%) patients had HR disease. T(4:14) was seen in 19/61 (31.1%) patients; t(14:16) in 9/61 (9.8%) patients; del 17p in 20/61 (32.7%) patients, 1q amp in 36/61 (59.0%) patients and 1p del + 1q amp in 8/61 (13.1%). Patients with more than one abnormality was seen in 22/61 (36.0%) patients. In this high-risk group, the most common induction regimen consisted of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in 58/61 patients (95.0%). 34 (55.7%) patients received single ASCT and 27 (44.2%) patients received tandem ASCT. 18/34 (52.9%) single ASCT patients and 15/27 (55.5%) tandem ASCT patients received maintenance therapy. Maintenance therapy included single-agent lenalidomide (imid) in 14/61 (22.9%); single-agent bortezomib or ixazomib (proteasome inhibitor (PI)) in 8/61 (13.1%), and; imid + PI combination in 11/61(18.0%). Baseline characteristics are summarized in Table 1.Single versus tandem ASCT in HR patients revealed no statistically significant PFS difference at 60 months (p=0.3). Maintenance therapy demonstrated a substantial improvement in PFS regardless of the number of ASCT (single ASCT HR=0.1687, 95% CI range 0.05-0.52, p<0.001) tandem ASCT (HR=0.1319, 95% CI range 0.01-0.96, p=0.019). PFS was similar in patients who did not receive maintenance in tandem ASCT (20 months) or single ASCT (19 months) (p=0.57).At the 60-month follow-up, the median PFS for high-risk patients without maintenance was 18.8 months. In contrast, the PFS for patients on maintenance was not reached (HR=0.1446, 95% CI range 0.05-0.38, p<0.001). There was no difference in OS (p=0.38) with or without maintenance therapy. When comparing single-agent vs. combination strategy with maintenance, there was no PFS (p=0.47) or OS (p=0.68) difference between strategies. All patients were progression-free in those who received any maintenance at 60 months.Conclusion: In our single centre experience, single vs. tandem ASCT in TE NDMM with HR disease did not contribute to long-term survival outcomes, but the presence of any maintenance therapy had a more considerable impact on PFS. Our data does show a longer progression-free survival compared to previous published data, which is likely due to our sample size. [Display omitted] DisclosuresLam: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Amgen: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria.

Use of an Antifibrinolytic Agent and Vitamin K As Alternative to Platelet Transfusions in Autologous Hematopoietic Cell Transplantation

BackgroundManaging thrombocytopenia with a prophylactic strategy was previously recommended for patients with impaired bone marrow function, hematological malignancies, and recipients of HCT when platelet counts declined to under 10,000/uL. However, the updated 2018 ASCO guidelines now suggest a place for a therapeutic i.e., after a bleeding event rather than a prophylactic platelet transfusion strategy for patients with hematologic malignancies undergoing autologous HCT. Studies show a lack of significant difference between trial groups in hemostatic outcomes, such as the number of WHO grade 2-4 bleeds, and number of days with bleeding events. Platelet transfusions increase risks of infectious and non-infectious complications as well as inducing a platelet refractory state. Our Transfusion Free Medicine Program has now performed over 200 autologous hematopoietic stem cell transplants (HCT) in Jehovah's Witnesses who due to religious convictions, do not accept red cell or platelet transfusions.Vitamin K is a fat-soluble vitamin that is required for normal blood clotting. Autologous HCT patients are at risk for vitamin K deficiency from multiple reasons including malnutrition, frequent use of antibiotics, chemotherapy induced gastrointestinal toxicity leading to malabsorption and colitis. The prothrombin test lacks the sensitivity and specificity to detect mild deficiency. A mild vitamin K deficiency may be underdiagnosed in our transplant patients adding to bleeding risk. With the effective use of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions we believe this may enhance hemostasis and prove a valuable adjunct to a therapeutic approach.MethodsPatients in our study were those who were of the Jehovah's Witness faith undergoing autologous HCT for Multiple Myeloma and Lymphoma. Patients received aminocaproic acid as an alternative to platelet transfusion to enhance hemostasis at a dose of 1 g every 4 hours or prophylactically for platelet counts less than 30,000 /uL. Titration to 4 g every 4 hours intravenously was required for platelet counts less than 10,000/ul or clinical bleeding. Vitamin K 10 mg orally or subcutaneous was also started at this time.ResultsTable 1 illustrates the low number of bleeding events especially grade 3 or 4 that occurred. There were no Grade 3 or 4 bleeding events in patients with platelet counts above 5000/uL. No patient had residual long term effects nor was there an increase in thromboembolic events.ConclusionsThese data add to the body of literature supporting a therapeutic platelet transfusion strategy in an experienced center for autologous HCT patients and challenges the prophylactic platelet count of 10,000 /uL suggesting instead 5000/uL. The safety and efficacy of antifibrinolytic agents and Vitamin K as an alternative to platelet transfusions to enhance hemostasis in autologous stem cell transplant patients may prove beneficial not only in JW patients but also in those transplant centers wishing to offer a therapeutic platelet transfusion approach and as a strategy to manage platelet refractoriness. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Aminocaproic Acid is an antifibrinolytic agent approved for treatment of bleeding in surgical patients and hematological bleeding disorders. Vitamin K is approved for use in reversal of anticoagulation from Warfarin, vitamin K deficiency without liver disease and in the newborn.

Addition of High-Dose Cytarabine to Immunochemotherapy before Autologous Stem-Cell Transplantation in Patients Aged 65 Years or Younger with Mantle Cell Lymphoma (MCL Younger): A Long-Term Follow-up of the Randomized, Open-Label, Phase 3 Trial of the European Mantle Cell Lymphoma Network

Addition of High-Dose Cytarabine to Immunochemotherapy before Autologous Stem-Cell Transplantation in Patients Aged 65 Years or Younger with Mantle Cell Lymphoma (MCL Younger): A Long-Term Follow-up of the Randomized, Open-Label, Phase 3 Trial of the European Mantle Cell Lymphoma Network

A Phase 2 Study of Extended Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma

A Phase 2 Study of Extended Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma

Outcomes of Tandem Hematopoietic Stem Cell Autologous Transplant in High-Risk Myeloma Patients: A Single-Center Experience

Introduction: Studies have demonstrated that multiple myeloma (MM) is a clinically, genetically complex and heterogeneous disease. Cytogenetic alterations identify high-risk patients in MM and are associated with a poor prognosis. They include at least one of the following at diagnosis: t(4;14), t(14;16), t(14;20), del(17p), 1q amp and 1q amp + del(1p). Autologous stem cell transplantation (ASCT) and the development of novel agents have considerably increased the median survival of MM patients. Patients with high-risk cytogenetics are associated with worse survival, and studies have shown improvement in progression-free survival with tandem ASCT when compared to single ASCT.Methods: This is a retrospective single-center study evaluating MM patients with high-risk cytogenetics at our center who have undergone a tandem autologous transplant from January 1, 2017, to December 31, 2020. Primary objective was overall response rates (ORR) and relapse rates. Secondary objectives looked at progression-free survival (PFS), overall survival (OS) using the Kaplan-Meier method.Results: From January 1, 2017, to December 31, 2020, 25 high-risk patients underwent tandem ASCT. Key patient characteristics are shown in table 1. Translocation (4:14) was seen in 8/25 (32%) patients; t(14:16) in 5/25 (20%) patients; del17p in 7/25 (28%), 1q amp in 8/25 (32%) patients, del1p + 1q amp in 5/25 (20%) patients. In terms of double hit and triple hit disease, 9/25 (36%) patients had two high risk changes and 3/25 (12%) with had three high risk changes. ISS staging wise, 5/25 (20%) patients were ISS stage I, 5/25 (20%) patients ISS stage 2 and 9/25 (36%) patients were ISS stage 3. The most common induction regimen consisted of cyclophosphamide, bortezomib, and dexamethasone (CyBorD). One patient each transitioned to daratumumab, lenalidomide and dexamethasone and PAD/CVD due to poor response. Maintenance therapy was given to 21/25 (84%) tandem ASCT patients with 5 (20%) patients receiving lenalidomide, 4 (16%) patients receiving proteasome inhibitor and 12 (48%) patients received dual maintenance.In terms of response, we recorded CR (complete response) vs VGPR (very good partial response) vs PR (partial response) after induction, 2-3 months after ASCT #1, 2-3 months after ASCT #2, 12 months after ASCT #2, and 12 months after maintenance. Following induction, 16 patients had achieved VGPR, and 9 of patients had achieved PR. After ASCT #1, 5 (55.5%) PR patients deepened their response to a VGPR. 1-3 months post ASCT #2, 3 (33.3%) PR patients deepened to a VGPR, and 2 (12.5%) VGPR patients achieved CR. 12 months after ASCT #2, 2 of the previous VGPR patients (12.5%) achieved CR, and 1 PR (11.1%) patient achieved VGPR.At the median follow-up time of 60 months, 44% of patients had relapsed. 1 patient relapsed within 1-3 months post ASCT#1. Nine other patients relapsed post ASCT #2 and maintenance except one patient who relapsed at time of ASCT #2. Univariable analysis identified hemoglobin as a statistically significant association with risk of progression or death. All patients who received any maintenance after tandem transplant were progression-free at 60 months (p<0.001).Conclusion: In our retrospective study, results suggest that tandem ASCT allows for deepening of responses. Together with maintenance therapy, this contributes to the durability of further PFS prolongation in high-risk MM patients. [Display omitted] DisclosuresLam: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Amgen: Honoraria. Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria.

INVESTIGATION OF DRUG-DRUG INTERACTIONS INVOLVING ANTI-INFECTIVE DRUGS IN PATIENTS UNDERWENT HEMATOPOIETIC STEM CELL TRANSPLANTATION

Drug-drug interactions are an important cause of adverse drug events. The preventable or manageable nature of drug-drug interactions puts them at the center of interventions. Since hematopoietic stem cell transplantation is a challenging and multi-drug process, drug-drug interactions are frequently encountered. In our study, the drugs used by a total of 100 patients with 50 autologous and 50 allogeneic bone marrow transplants for 10 days before transplantation, on the day of transplantation and for 10 days after transplantation were examined retrospectively in terms of interaction. Two paid softwares and two free softwares were used to examine interactions. The obtained data were analyzed with Microsoft Excel program. A total of 3805 interactions were observed in the 21-day period in 50 patients who underwent allogeneic stem cell transplantation, and these interactions occurred with the repetition of 1017 interactions in different patients. For the same period in 50 autologous stem cell transplant patients, 2906 interactions were detected, and this number occurred with 725 different interactions seen in different patients. It has been understood that anti-infectives cause serious interaction load. Hematopoietic stem cell transplantation is a period in which prophylactic or anti-infective treatment for the detected microorganism is applied intensively. Interactions of anti-infectives with each other and with other drugs in the treatment regimen are frequently encountered during the transport process. Interactions should be identified and their clinical significance should be demonstrated. It should be handled with the partnership of physician-clinical pharmacist.

The effect of comorbidity on survival and collected CD34 + cell counts in autologous hematopoietic stem cell transplant patients

ObjectiveIn this study, we aimed to report the effectiveness of hematopoietic cell transplantation–specific comorbidity index (HCT-CI) and GATMO scores in predicting overall survival (OS) who underwent autologous stem cell transplantation (ASCT). Material and methodsThe data of 263 MM and 204 lymphoma patients who underwent ASCT in the last 11 years were retrospectively analyzed. ResultsNeutrophil engraftment time, thrombocyte engraftment time and collected CD34+ cell counts were similar in MM patients with HCT-CI>2 and HCT-CI≤2 (all p>0.05). Although the estimated median OS of MM patients with HCT-CI ≤2 tended to be higher than those with HCT-CI>2, this difference was not statistically significant (52.8 vs 45 months, p=0.172). No effect of GATMO score on CD34 + count, engraftment times and OS in MM patients was detected (p>0.05). The effect of HCT-CI score on lymphoma patients was examined, it was found that the neutrophil engraftment time was longer (p=0.039) and the number of collected CD34+ cells was lower (p=0.02) in patients with HCT-CI>2 than those with HCT-CI≤2. While the estimated median OS of lymphoma patients with HCT-CI≤2 was 51.5 months, the estimated median OS of patients with HCT-CI>2 was 9.5 months (p=0.012). When lymphoma patients were divided into four groups according to their GATMO scores, the OS of the four groups was found to be different from each other (p<0.001). ConclusionHCT-CI and GATMO scores predict OS in lymphoma patients but not MM patients.

Immune Reconstitution following High-Dose Chemotherapy and Autologous Stem Cell Transplantation with or without Pembrolizumab Maintenance Therapy in Patients with Lymphoma

Autologous stem cell transplantation (ASCT) is a standard of care for patients with chemosensitive, relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) and diffuse large B cell lymphoma (DLBCL). Whereas the clinical benefit of ASCT has traditionally been attributed solely to cytoreduction from intensive chemotherapy, ASCT has important immunogenic effects that may contribute to its antitumor efficacy and could provide a favorable immune environment for post-ASCT immune-based maintenance treatments. We previously reported clinical results of a phase II trial (ClinicalTrials.gov identifier NCT02362997) testing 8 doses of pembrolizumab maintenance therapy after ASCT for patients with R/R cHL or DLBCL. To clarify the impact of pembrolizumab on immune reconstitution, we compared the kinetics of peripheral blood immune cell recovery after ASCT for trial patients receiving pembrolizumab maintenance to those of a contemporaneous control cohort of similar patients undergoing ASCT without pembrolizumab maintenance. This study was conducted to characterize the impact of post-ASCT pembrolizumab maintenance therapy on immune reconstitution for patients with R/R DLBCL and cHL and to identify candidate biomarkers of efficacy and immune-related adverse events (irAEs). Peripheral blood (PB) mononuclear cell samples were prospectively collected at 1 to 18 months after ASCT and analyzed by flow cytometry using a panel of fluorophore-conjugated monoclonal antibodies to identify B cells, natural killer (NK) cells, and various dendritic cell (DC) and T cell subsets. A median of 5 (range, 1 to 8) post-ASCT PB samples were collected from 144 patients (59 in the pembrolizumab group and 85 in the control group). Clinical characteristics of the 2 cohorts were similar. Compared with cHL patients, DLBCL patients (all of whom received anti-CD20 monoclonal antibody therapy before ASCT) had delayed CD19+ cell reconstitution that persisted for at least 18 months after ASCT. No other differences in immune reconstitution based on lymphoma subtype were observed. Post-ASCT pembrolizumab maintenance therapy was associated with an elevation in circulating DCs (driven by higher levels of plasmacytoid and immature DCs) that persisted for the duration of pembrolizumab treatment, along with a significant reduction in PD-1+ T cells that persisted for 6 to 12 months after completion of pembrolizumab therapy. Despite the key role of T cells in mediating the effects of PD-1 blockade, pembrolizumab maintenance did not affect recovery of any T cell subsets. In an exploratory analysis, a higher baseline CD4+ terminal effector memory cell count (defined as CD3+CD4+CD45RA+CD62L-) was associated with inferior progression-free survival (PFS), but only among patients who received pembrolizumab maintenance (P=.003). As continuous variables, lower absolute levels of NK cells (P=.009), PD-1+ CD4+ T cells (P=.005), and PD-1+ CD8+ T cells (P=.005) before pembrolizumab initiation were each associated with a higher risk of grade 2+ irAEs. Our findings indicate that post-ACST pembrolizumab maintenance therapy is associated with a persistent elevation of circulating DCs, but its impact on the reconstitution of other immune cells in peripheral blood appears limited. Our study suggests that early features of post-ASCT immune reconstitution could be associated with PFS and the risk of irAE and warrant additional investigation. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Daratumumab for post-ASCT maintenance treatment of myeloma.

Daratumumab, a potent CD38-directed monoclonal antibody, has veritably transformed the treatment landscape of multiple myeloma. 1 Nooka AK Kaufman JL Hofmeister CC et al. Daratumumab in multiple myeloma. Cancer. 2019; 125: 2364-2382 Crossref PubMed Scopus (58) Google Scholar CASSIOPEIA, a two-part, phase 3 trial, has brought daratumumab to the forefront of efforts aimed at improving outcome for transplant-eligible patients. 2 Moreau P Attal M Hulin C et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019; 394: 29-38 Summary Full Text Full Text PDF PubMed Scopus (346) Google Scholar Part 1 randomly assigned 1085 patients with newly diagnosed multiple myeloma to receive four pre-autologous stem-cell transplantation (ASCT) induction and two post-transplant consolidation cycles of bortezomib, thalidomide, and dexamethasone (VTd) alone, or in combination with daratumumab (D-VTd). D-VTd showed considerable improvement in depth of response and progression-free survival, leading to its regulatory approval. 2 Moreau P Attal M Hulin C et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019; 394: 29-38 Summary Full Text Full Text PDF PubMed Scopus (346) Google Scholar An improved overall survival with D-VTd became apparent with longer follow-up. 3 Moreau P Hulin C Perrot A et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021; (published online Sept 13.)https://doi.org/10.1016/S1470-2045(21)00428-9 Google Scholar A more contemporary regimen, D-VRd, involving lenalidomide, is awaiting mature data. 4 Voorhees PM Kaufman JL Laubach J et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020; 136: 936-945 Crossref PubMed Scopus (169) Google Scholar Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trialDaratumumab maintenance every 8 weeks for 2 years significantly reduced the risk of disease progression or death compared with observation only. Longer follow-up and other ongoing studies will shed further light on the optimal daratumumab-containing post-ASCT maintenance treatment strategy. Full-Text PDF

P-186: Toxicity and survival outcomes of autologous stem cell transplant in Multiple Myeloma patients with renal impairment

<h3>Background</h3> High dose therapy followed by autologous stem cell transplant (ASCT) remains a standard of care for eligible patients with multiple myeloma(MM) as it has been shown to deepen responses and prolong progression-free survival (PFS). There is some evidence to support the use of ASCT in patients with renal impairment and is recommended by IMWG for the management of MM in renally impaired patients. Some of the studies however, have shown increased risks associated with ASCT, coupled with somewhat poorer outcomes in this group of patients. Through this multicentre retrospective study, we demonstrate the feasibility of ASCT in patients with renal impairment (creatinine clearance <60ml/min) and document the safety, PFS and overall survival (OS) of this cohort, in comparison to patients who did not have renal impairment immediately prior to ASCT (CrCl≥60ml/min). <h3>Methods</h3> Patients with MM who had renal impairment at diagnosis who underwent ASCT between 2010-2018 were identified from the institutional disease registries. They were then stratified into 2 groups – the first cohort had renal impairment at diagnosis and at ASCT while the second cohort had renal impairment at diagnosis but with normal renal function prior to ASCT. The patient characteristics, safety and survival outcomes were collected and the data was analysed using STATA. A total of 50 patients were identified, 38 patients had renal impairment and 12 patients had normal renal function prior to ASCT. There was no difference in the baseline characteristics between both groups, including age, sex, prognostic scores (ISS, R-ISS), first line induction therapy, best response to first line therapy and mean peripheral blood stem cells collected. <h3>Results</h3> There was increased incidence of grade 3 or 4 neutropenia during ASCT (100% vs 83.3%, p=0.00) in the cohort of patients with renal impairment. However, this did not translate to increased febrile neutropenia episodes (73.7% vs 91.7%, p=0.19), or prolonged admission (20.7 vs 22.7 days, p=0.97). The incidences of serious grade 3 or 4 adverse events such as anaemia, thrombocytopenia, diarrhoea and vomiting were not different between both cohorts. The dose of melphalan used for ASCT was attenuated in patients with renal impairment (133mg VS 197mg, p=0.02). Despite this difference, the mean number of days taken for neutrophil and platelet engraftment were similar (11.0 vs 12.1 days p=0.02 and 14.1 vs 13.1days, p=0.97 respectively). Overall outcomes also did not differ between patients with renal impairment vs normal renal function, with comparable 3-year PFS (60.5% VS 58.3%, p=0.849) and 3- year OS (78.9% VS 83.3%, p=0.86). <h3>Conclusion</h3> Taken together, our cohort of patients with renal impairment had comparable toxicity profiles and overall outcomes as compared to patients with normal renal function. As such, ASCT should be considered in patients who present with renal impairment in line with the international recommendations so as to optimise their long-term outcomes.

P-118: Relapse with plasmacytoma after upfront autologous stem cell transplantation in multiple myeloma

<h3>Background</h3> Plasmacytoma has been reported to be associated with poor prognosis in patients with multiple myeloma (MM). In this study, we evaluated the incidence of plasmacytoma and survival outcomes in newly diagnosed MM who underwent upfront autologous stem cell transplantation (ASCT). <h3>Method</h3> This study retrospectively analyzed the data of 303 patients with MM who underwent upfront ASCT between April 2000 and April 2018 from 8 institutes in Korea. A total of 52 patients (17.1%) had plasmacytoma at relapse after upfront ASCT. Of them, 27 patients showed paramedullary plasmacytoma (PMD) and 25 patients showed extramedullary plasmacytoma (EMD). <h3>Results</h3> Patients with plasmacytoma at initial diagnosis had more plasmacytoma at relapse than those without plasmacytoma (37.1% vs. 11.2%). Over a median follow-up of 66.0 months, patients with plasmacytoma at relapse had significantly inferior overall survival (OS) than those without plasmacytoma (43.9months vs. 100.7 months, P <0.001), but the OS did not significantly differ between patients with EMD and those with PMD (56.6 months vs. 42.2 months, P=0.464). After relapse, all patients received salvage therapy with borteozmib or lenalidomide-based regimen, but progression free survival (PFS) after relapse was significantly shorter in patients with plasmacytoma than those with no plasmacytoma (6.4 months vs. 12.4 months, P <0.007). <h3>Conclusion</h3> This study showed that plasmacytoma was frequently developed at relapse after upfront ASCT in patients with plasmacytoma at initial diagnosis and plasmacytoma at relapse was significantly associated with poor prognosis.

A Multicenter Study of Clinical Presentations and Outcomes of Multiple Myeloma in Pakistan: The Real-World Analysis in a Resource-Constrained Country.

This is the first multicenter study from Pakistan exploring the prevalence, clinical presentations and treatment outcomes of Multiple Myeloma patients. This retrospective study involved data collection from hospital record system of four tertiary care referral hospitals of Pakistan including all patients diagnosed as having Multiple Myeloma from January 2014 to December 2018. The demographic details, clinical presentations, laboratory findings, treatment responses, and mortalities were evaluated. The progression-free survival and overall survival were analyzed considering relapse and mortality as the end points, respectively. For the progression-free survival, the Kaplan-Meier survival analysis and the log rank test were used to compare the survival function for chemotherapy followed by autologous stem cell transplant (ASCT) as opposed to chemotherapy alone (non-ASCT). The overall survival analysis was assessed by Kaplan-Meier survival analysis. This study identified 403 Multiple Myeloma patients in five years. The median age at presentation was 55years. Bortezomib based drug regimens were the most commonly used initial treatments (57.5%). Forty three patients received ASCT. The progression-free survival median for ASCT and non-ASCT patients were 50months (95% CI, 42-57.9months) and 26months (95% CI, 21.5-30.5months), respectively. The cumulative probability of survival rate at 60months was 80%. This study identified 403 Multiple Myeloma patients over 5years in four tertiary care hospitals of Pakistan. It underscores the importance of autologous stem cell transplant in Myeloma patients and advocates improving its facilities in Pakistan.

Editorial introductions.

Editorial introductions.

Autologous Stem-Cell Transplantation in Patients with Multiple Myeloma

Introduction: Multiple myeloma is a cancer of the plasma cells that attacks and destroys bones. Myeloma is the second most common cancer of the blood and accounts for about 12% of diagnosed hematologic cancers. Depending on the patient's condition and age, the treatment of multiple myeloma aims to eliminate the manifestations of the disease, to contain its progression and/or to treat the complications to ensure a better patient's quality of life. The survival rate in multiple myeloma patients is significantly improved through new therapeutic agents such as monoclonal antibodies, immunomodellers, proteasome inhibitors and hematopoietic stem cells transplantation, which is considered as the standard protocol in patients under 65 years old. The objective of this study is to determine the importance of autologous hematopoietic stem cell transplantation in improving the survival rate and quality of life of patients with multiple myeloma. Materials and methods: 319 multiple myeloma patients who underwent hematopoietic autologous stem-cell transplantation, were included in this retrospective descriptive and analytical study. Results: multiple myeloma can affect both sexes, the results of our study revealed a male predominance with a percentage of 61%. Dataanalysis shows a significant correlation between the patient's age and the CD 34+ count and a highly significant correlation between cryotherapy and overall survival rate that was about 5 years. Conclusion: through our study, we have confirmed that autologous transplantation strongly contributes to improving the survival rate of myeloma patients. Hematopoietic stem-cell transplantation remains the first-line treatment for patients under 65 years of age.

The Effect and the Cost of Tandem Transplantation in Multiple Myeloma Patients with Adverse Cytogenetics

Introduction:Autologous stem cell transplantation (ASCT) plays a major role in the treatment of multiple myeloma. However, the result of STaMINA trial showed no extra benefit of second transplantation or consolidation therapy in addition to single ASCT; there is still argue about the optimal intensity of the treatment in patients with high-risk cytogenetic abnormalities. We analyzed retrospectively, the effect of the tandem ASCT and the cost.Methods:We analyzed multiple myeloma patients with Adverse Cytogenetics who were treated with ASCT in National Center for Global Health and Medicine Hospital from January 2010 to the end of March 2017. Most patients were treated with bortezomib based induction therapy. Patients who failed to achieve very good partial remission or better after the first ASCT proceeded to the second ASCT. Most patients received consolidation therapy and/or maintenance therapy. Overall Survival (OS) and progression free survival (PFS) was analyzed using the Kaplan-Meier methods, and the log-rank test. Also, cumulative cost for the treatment was evaluated. Adverse cytogenetics were defined as hypodiploidy, del(17p), t(4;14), and t(14;16).Results:Ten patients were treated with tandem ASCT, and fifteen patients were treated with single ASCT. Twenty-one patients were treated with BD regimen, two patients with CyBorD regimen, and two patients with VAD regimen. The median number of induction therapy was 4 cycles (4-6). The PFS of the tandem ASCT group (3yrs PFS was 87.5%) was superior to the single ASCT group (3yrs PFS was 37.2%) (P = 0.0038). The OS of the tandem ASCT group (3yrs PFS was 100%) was superior to the single ASCT group (3yrs OS was 49.5%) without statistical significance (P = 0.057). We compared cumulative costs of tandem ASCT patients with single ASCT patients. We plotted the average cumulative cost of every 3 months in each group. The first 21 months and beyond 54 months, the rate of cost increment was apparently higher in the single ASCT group than tandem ASCT group. A regression line was calculated for the average cumulative cost of single ASCT group and tandem ASCT group. Regression analysis revealed that overall inclination of the regression line of the cost in single ASCT was significantly larger than that of the cost in tandem ASCT (P = 0.0024).Conclusion:The outcome of tandem ASCT was superior to single ASCT in patients with adverse cytogenetics. Also, the total cost in patients with tandem ASCT was lower than that with single ASCT. Tandem ASCT may reduce the rate of relapse and the cost for salvage treatment. Therefore, tandem ASCT should be considered for multiple myeloma patients with adverse cytogenetics from a cost-benefit point of view. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.