scholarly journals Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome–Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study

2017 ◽  
Vol 35 (16) ◽  
pp. 1795-1802 ◽  
Author(s):  
Giovanni Martinelli ◽  
Nicolas Boissel ◽  
Patrice Chevallier ◽  
Oliver Ottmann ◽  
Nicola Gökbuget ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Response ◽  
Minimal Residual

Purpose Few therapeutic options are available for patients with Philadelphia chromosome–positive (Ph+) B-precursor acute lymphoblastic leukemia (ALL) who progress after failure of tyrosine kinase inhibitor (TKI) −based therapy. Here, we evaluated the efficacy and tolerability of blinatumomab in patients with relapsed or refractory Ph+ ALL. Patients and Methods This open-label phase II study enrolled adults with Ph+ ALL who had relapsed after or were refractory to at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. Blinatumomab was administered in 28-day cycles by continuous intravenous infusion. The primary end point was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first two cycles. Major secondary end points included minimal residual disease response, rate of allogeneic hematopoietic stem-cell transplantation, relapse-free survival, overall survival, and adverse events (AEs). Results Of 45 patients, 16 (36%; 95% CI, 22% to 51%) achieved CR/CRh during the first two cycles, including four of 10 patients with the T315I mutation; 88% of CR/CRh responders achieved a complete minimal residual disease response. Seven responders (44%) proceeded to allogeneic hematopoietic stem-cell transplantation, including 55% (six of 11) of transplantation-naïve responders. Median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively. The most frequent AEs were pyrexia (58%), febrile neutropenia (40%), and headache (31%). Three patients had cytokine release syndrome (all grade 1 or 2), and three patients had grade 3 neurologic events, one of which (aphasia) required temporary treatment interruption. There were no grade 4 or 5 neurologic events. Conclusion Single-agent blinatumomab showed antileukemia activity in high-risk patients with Ph+ ALL who had relapsed or were refractory to TKIs. AEs were consistent with previous experience in Ph– ALL.

Allogeneic hematopoietic stem cell transplantation contributes to eradication of minimal residual disease in adult Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with dasatinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7024-7024
Author(s):  
Jeremy Chang ◽  
Mojtaba Akhtari
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Minimal Residual

7024 Background: Philadelphia Chromosome-Positive (Ph+) disease is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). Recent studies have shown that the eradication of minimal residual disease (MRD) in this population leads to improved survival outcomes. While hematopoietic stem cell transplantation (HSCT) has demonstrated clinical benefits in Ph+ ALL patients treated with the tyrosine kinase inhibitor (TKI) imatinib, its role is less clear with the use of more potent, newer-generation TKIs such as dasatinib. Methods: This was a retrospective study analyzing the impact of allogeneic HSCT on MRD status in Ph+ ALL patients treated with dasatinib. Patients were divided into 2 groups: those treated with chemotherapy plus dasatinib followed by allogeneic HSCT and those who received chemotherapy plus dasatinib alone. All patients underwent bone marrow biopsy with MRD analysis following induction therapy and subsequent re-evaluation of MRD status at day 100 post-transplant in the HSCT group and after further cycles of chemotherapy plus dasatinib in the non-transplant group. MRD-negative disease was defined as the absence of a BCR-ABL1 transcript by real-time quantitative polymerase chain reaction (qRT-PCR) with a sensitivity of 0.01%. Results: A total of 51 adult Ph+ ALL patients with MRD-positive disease following induction therapy were included. Twenty-seven patients (53%) were male and the median age at time of diagnosis was 42 years (range 23-68). There were 29 patients in the transplant group and 22 patients in the non-transplant group. When analyzing rates of MRD eradication, 18 (62%) patients in the transplant group were found to have MRD-negative disease at day 100 post-transplant compared to 7 (32%) patients in the non-transplant group who only received further cycles of chemotherapy plus dasatinib (risk ratio 0.56, 95% confidence interval 0.32-0.96, p = 0.048). Conclusions: In the era of newer-generation TKIs, allogeneic HSCT continues to have notable benefits in Ph+ ALL such as a significantly higher rate of MRD eradication as demonstrated in this study.

Conditioning with 8 Gy Total Body Irradiation and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia: Projected 4-Year Update.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3016-3016
Author(s):  
Matthias Stelljes ◽  
Martin Bornhaeuser ◽  
Matthias Kroger ◽  
Joerg Beyer ◽  
Maria C. Sauerland ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Dna Typing ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Unrelated Donors ◽  
Total Body ◽  
Acute Myeloid

Abstract Seventy-one patients with acute myeloid leukemia (AML), most of them (63/71) considered ineligible for conventional allogeneic hematopoietic stem cell transplantation (HSCT), were enrolled into a phase II study on reduced intensity myeloablative conditioning with fractionated 8 Gy total body irradiation (TBI) and fludarabine (120 mg/m2) (Blood. 2005 Nov 1;106(9):3314–21). Patients received mobilized peripheral blood stem cells (n=68) or bone marrow (n=3) from siblings (n=39) or unrelated donors (n=32). HLA-typing was performed for HLA-A, -B, -Cw (serological matching or intermediate resolution DNA typing), DRB1 and DQB1 (high resolution DNA typing). Three patients had unrelated donors with an allele mismatch in HLA DRB1 (2 with an additional mismatch in HLA Cw) and 7 patients were transplanted from unrelated donors with an antigen mismatch in HLA Cw. Thirty-six patients were transplanted in complete remission (CR) and 35 with untreated or refractory disease (non-CR). Median patient age was 51 years (range, 20–66). Sustained engraftment was attained in all evaluable patients. With a median follow-up of now 41.3 months (range, 20.4–70.4) in surviving patients, probabilities of overall survival for patients transplanted in CR and non-CR were 80% (95% CI, 66 to 94%) and 17% (95% CI, 5 – 29%) at 4 years, respectively. Relapse-free survival rates were 57% (95% CI, 39 – 75%) and 14% (95% CI, 2 – 26%). Of the 35 evaluable patients transplanted in CR, 10 patients suffered a relapse between days 68 and 868 after transplantation (cumulative incidence 29%). Five patients with late relapse (>1 year after transplantation) achieved a subsequent CR after conventional chemotherapy, blood stem cell boost and treatment with granulocyte-macrophage colony-stimulating factor, lasting 2000+, 1841+, 909+, 847+ and 480 days, respectively. Depending on donor type, relapse-free survival was similar in patients transplanted from unrelated or sibling donors. Overall survival in patients transplanted in complete remission from unrelated vs. sibling donors was 84% (95% CI, 73 – 95%) vs. 77% (95% CI, 68 – 86%). The cumulative incidence of non-relapse mortality (NRM) in CR patients was 11% at 4 years and beyond (3 patients deceased before day 100 and 1 patient 25 months after transplantation), but amounted to 37% at 4 years in non-CR patients. Nine of the 33 surviving patients (27%) have actually active chronic GvHD (5 limited and 4 extensive disease). This update confirms that allogeneic HSCT from related or unrelated donors with 8 Gy TBI/fludarabine conditioning is feasible with low NRM and preserved long-term antileukemic activity in AML patients in first or later CR.

Significance of Minimal Residual Disease in Patients with Chronic Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3269-3269
Author(s):  
Iwona Solarska ◽  
Barbara Nasilowska-Adamska ◽  
Maria Bieniaszewska ◽  
Jan Maciej Zaucha ◽  
Piotr Rzepecki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Chronic Phase ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Low Level ◽  
High Level ◽  
Minimal Residual

Abstract Abstract 3269 Poster Board III-1 Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for patients (pts) with chronic myeloid leukemia (CML). AlloHSCT is associated with long-term disease-free survival in 40% to 80% pts transplanted in early chronic phase of disease. The probability of relapse for pts transplanted in first chronic phase is 10% to 20% at 5 years, and is even higher (30% – 60%) for pts who received transplant in advanced phases of CML. The significance of minimal residual disease (MRD) in this clinical setting is uncertain. We enrolled 63 consecutive pts with CML who had received an alloHSCT between 1995 and 2007 and had BCR-ABL transcript quantity measured by RQ-PCR method on at least 2 occasions during follow-up in the period starting 6 months after alloHSCT. The reverse transcription was preformed using SuperScriptIII and random hexamers. Quantification of BCR-ABL was performed by RQ-PCR assay according to ‘Europe Against Cancer' protocol. BCR-ABL expression was normalized with endogenous control ABL gene and expressed as a ratio BCR-ABL/ABL. According to the amount of BCR-ABL transcript detected in blood or bone marrow after alloHSCT pts were allocated into 3 categories, including pts with no-detectable or stable very low-level of BCR-ABL transcripts (ratio BCR-ABL/ABL below 0.005%), pts with fluctuating-low level of BCR-ABL transcripts (0.005 – 0.01%) and pts with high-level of BCR-ABL transcripts (0.01 – 0.1%). We didn't find any relationships between different BCR-ABL levels after alloHSCT and clinical parameters at the time of CML diagnosis or transplantation, including Sokal, Hasford and Gratwohl scores. Median time from alloHSCT to molecular relapse (MR) was 38 months (range, 8.5 – 88.5 months). The 3-year progression rate into cytogenetic or hematological relapse of CML since MR was 70%. This progression occurred at a median time of 1.4 months (range, 0 – 3.2 months). We found strong correlation between the levels of BCR-ABL transcripts after alloHSCT and a risk of relapse. The incidence of MR was 0%, 26%, 71% for the low-level, fluctuating-low level and high-level of BCR-ABL transcript (p<.0001), respectively. Similarly the risk of cytogenetic and hematological relapse was 0%, 21%, 43% for these pts (p=.001), respectively. Five-year leukemia-free survival was 100%, 83.9% and 66.7% for the pts with low-level, fluctuating-low level and high-level BCR-ABL transcript (p=.003), respectively. There was no apparent relationship between the level of BCR-ABL transcript and overall survival. We conclude that pts with fluctuating-low and/or high levels of BCR-ABL transcripts are at higher risk of disease progression. Sequential RQ-PCR monitoring coupled with pre-emptive therapy can provide a valid strategy to reduce rates of relapse and development of a more individualized approach to management of pts with CML in major molecular response after alloHSCT. Disclosures: Warzocha: BMS: Consultancy, Honoraria; Celgene: Consultancy; Roche: Honoraria; Pfizer: Honoraria; Amgen: Honoraria.

scholarly journals Clinical Implication of BCR/ABL Fusion Transcript Monitoring in Addition to Ig/TCR Gene Rearrangement-Based Minimal Residual Disease in Philadelphia Chromosome-Positive Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2258-2258
Author(s):  
Kirsten Bleckmann ◽  
Julia Alten ◽  
Anja Moericke ◽  
Andishe Attarbashi ◽  
Andrea Teigler-Schlegel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Fusion Transcript ◽  
Minimal Residual

Abstract Background: Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for about 3% of pediatric ALL and has a poor prognosis. Advances of treatment due to the tyrosine kinase inhibitor imatinib have improved the cure rates. According to recent guidelines in the amended European intergroup trial on Ph+ ALL (EsPhALL), patients with rapid minimal residual disease (MRD) response and negativity during further treatment are no longer eligible for allogeneic stem cell transplantation (alloSCT). This down-grading of therapy in a circumscribed patient cohort with favorable prognosis is a desirable development as stem cell transplantation still implies a considerable risk of toxicity. These guidelines refer to MRD by immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and do not consider monitoring of the BCR/ABL fusion transcript as long as informative results for Ig/TCR MRD are available. However, discrepancies between the results of the two methods occur. This complicates the decision on alloSCT indication if Ig/TCR MRD becomes negative while the BCR/ABL fusion transcript remains detectable. Objectives/Methods: We therefore evaluated the prognostic relevance of this specific combination of findings, i.e. the continuous negativity for Ig/TCR MRD and persistently positive results for BCR/ABL after the second intensive consolidation block or later, in 16 pediatric patients with Ph+ ALL. They were identified among 139 German and Austrian Ph+ patients treated in the ALL-BFM 2000 or EsPhALL trial from August 1, 1999 to July 31, 2013. Twelve out of the 16 patients received imatinib in first-line treatment intermittently as previously described in the EsPhALL protocol (Biondi A et al Lancet Oncol. 2012) or continuously as recommended by the amended EsPhALL protocol. Results: Eight of the 16 identified patients received an alloSCT in first complete remission (1st CR), whereas the remaining eight patients were treated with chemotherapy only. Of the eight patients with alloSCT, seven are in first continuous complete remission (1st CCR) with median EFS of 7.6 years, one patient died after second relapse. In the group of eight patients without alloSCT three are in 1st CCR with a median EFS of 2.6 years, four patients are in 2nd CR after relapse (3/4 had alloSCT in 2nd CR, median EFS 4.7 years), and one patient with Down syndrome died of an infectious complication. Remarkably, two patients of the latter group (both with M-BCR) showed a protracted increase of BCR/ABL copy numbers over several years with neither morphological signs of relapse nor Ig/TCR MRD based reappearance. One of them eventually suffered a relapse 5 years after diagnosis, one is still in 1st CCR with EFS of 5.2 years. Conclusion: The data suggest that patients with Ig/TCR MRD negativity and persistently detectable BCR/ABL fusion transcript have a high risk of relapse when treated with chemotherapy only and may benefit from alloSCT. However, patient numbers are currently too small to deduce recommendations from this observation. Further investigation of a larger cohort with longer follow-up is needed to confirm the prognostic importance of BCR/ABL fusion transcript monitoring in addition to Ig/TCR MRD, especially considering a potential additional impact of the recently implemented continuous imatinib treatment. One additional patient would have met the diagnostic inclusion criteria of this analysis. He had an extensive increase of BCR/ABL fusion transcript at the end of maintenance treatment while being in morphological remission and negative for Ig/TCR MRD. This patient proved to be BCR/ABL positive in granulocytes revealing a chronic myeloid leukemia (CML) misdiagnosed as ALL during initial blast crisis. This indicates that an underlying CML might be taken into consideration also in other patients of the analyzed cohort. In consequence, BCR/ABL in granulocytes is now tested in all newly diagnosed Ph+ ALL patients in Germany to ensure the differentiation of BCR/ABL positive ALL vs. CML in blast crisis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic Role of Minimal Residual Disease before and after Hematopoietic Stem Cell Transplantation in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1413-1413
Author(s):  
Bartolomeo Rossi ◽  
Mimma Campeggio ◽  
Elisa Magrin ◽  
Marco Zecca ◽  
Laura Rubert ◽  
...  
Keyword(s):  
Stem Cell ◽  
Poor Prognosis ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Good Prognosis ◽  
Prognostic Role ◽  
Hematopoietic Stem ◽  
Before And After ◽  
Minimal Residual

Abstract Background and Objectives Currently, more than 80% of children with acute lymphoblastic leukemia (ALL) can be cured through intensive and risk-adapted chemotherapy protocols. Allogeneic hematopoietic stem cell transplantation (HSCT) is considered beneficial for approximately 10% of the patients who are at very-high risk at frontline therapy and for the majority of patients after relapse. In this retrospective study, we aimed to assess the prognostic role of minimal residual disease (MRD) before HSCT and at different time points after transplantation in children with ALL. Patients and Methods We analyzed 64 pediatric ALL patients given HSCT: 22/64 were in first complete remission (1CR) and 42/64 in second complete remission (2CR). Genomic DNA was obtained from bone marrow aspirates collected at diagnosis/relapse, before HSCT (pre-HSCT) and at the first and third trimesters after HSCT (post-HSCT1 and post-HSCT3). MRD was measured by quantitative real-time PCR assays based on patient-specific junctional regions and interpreted according to the EuroMRD guidelines. The association between MRD and survival was assessed by chi-square test. Results All evaluated patients were analyzed for MRD before transplantation (pre-HSCT). MRD was negative in 26/64 patients and positive in 38/64 patients. As for cases with positive MRD, 17/38 showed MRD levels ≥1x10-3 and 21/38 <1x10-3. Any detectable MRD positivity at pre-HSCT was significantly associated with a poor prognosis: 28/38 patients with positive MRD are dead, whereas 22/26 with negative MRD are alive in CR (P < 0.001). Among the 42 patients in 2CR, 14/42 had negative pre-HSCT MRD and 28/42 were MRD positive. The negativity of MRD before transplantation was found to be significantly associated with a good prognosis: 13/14 patients with negative MRD are alive in CR, while 23/28 with positive MRD are dead (p < 0.001). Post-HSCT1 MRD was analyzed in 53 patients: 17/53 were MRD positive and 36/53 were MRD negative. Based on MRD status, the prognosis was significantly different: 26/36 patients with negative post-HSCT1 MRD are alive in CR, whereas 14/17 of patients with positive MRD are dead (P < 0.001). Post-HSCT3 MRD was assessed in 41 patients and 19/41 were found positive. Persistence of MRD was associated with a poor prognosis also at this time-point (P = 0.001). Conclusions These results confirm that MRD assessment has a critical role both before and after transplantation. Negative MRD before transplantation is strongly associated with a good prognosis, particularly in 2CR patients. Since persistence of MRD after HSCT is significantly associated with a worse outcome, these patients could benefit from early discontinuation of immunosuppression, adoptive T-cell therapy and use of new drugs. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Impact of HLA Mismatch Direction on the Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in AML Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4608-4608
Author(s):  
Wen-Chun Chen ◽  
Jyh-Pyng Gau ◽  
Liang-Tsai Hsiao ◽  
Chia-Jen Liu ◽  
Yao-Chung LIU ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Matched Group ◽  
The Impact

Background: For patients with acute myeloid leukemia (AML) who were classified as high risks, failed to achieve complete remission, or relapsed disease after remissions, allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers the chance of durable remission and the potential to cure. In the absence of 8/8 matched donors, an HLA 1-allele mismatched (7/8 1-MM) unrelated donor is an alternative source of hematopoietic stem cell. However, the impact of HLA homozygosity at 1-MM on the outcome and the consensus at desirable donor screening in 7/8 HLA mismatched is not yet clear. A 1-MM in the host-versus-graft (HVG) direction is a 7/8 unidirectional mismatch for a homozygous recipient receiving a graft from a heterozygous donor. A 1-MM in the graft-versus-host (GVH) is for a heterozygous recipient receiving a graft from a homozygous donor. 7/8 bidirectional mismatch is a heterozygous recipient receiving a graft from heterozygous donor. From the biological perceptions, the impact of different histocompatibility transplantations may differ on the prognosis. This study evaluated the outcome of unidirectional and bidirectional 7/8 mismatches in recipients receiving either bone marrow or peripheral blood hematopoietic stem cell for AML patients. Methods: Patients who were at least 12 years of age with AML receiving first hematopoietic stem cell transplantation from a serologically HLA-A, -B, -C, and -DR allele data were included in our study between 2009 and 2014. Data were obtained from Taiwan Society of Blood and Marrow Transplantation (TBMT) Research Database. We excluded those who received HLA-matched sibling grafts, HLA-haploidentical grafts, or unrelated donors who had more than 1-allele mismatch. Those who lacked the clinical information on survival status or survival date were also eliminated. Patients were divided into four histocompatibility groups based on typing at HLA-A, -B, -C, and -DR as unidirectional 7/8 HVG, unidirectional 7/8 GVH, bidirectional 7/8, and 8/8 matched group. Descriptive statistics were used to describe the patients' characteristics, disease status on the time receiving HSCT, intensity of conditioning regimen and treatment features. Associations between four groups and outcomes of overall survival, relapse-free survival, acute GVHD, chronic GVHD, treatment-related mortality (TRM), relapse rate, neutrophil engraftment, engraftment syndrome, and engraftment failures were reviewed. Results: A total of 222 recipients of all-HSCT were included in the analysis. The four comparison groups included nine patients designated as 1-MM HVG, nine as 1-MM GVH, 71 as 1-MM bidirectional, and 133 as 8/8 matched group. Table 1 shows patient and transplant characteristics. Superior overall survival was significantly associated with the higher intensity of induction regimen (myeloablative conditioning, MAC and reduced intensity conditioning, RIC, p<0.05) and the disease status on the time receiving allo-HSCT (p=0.1). Relapse-free survival was significantly decreased with RIC regimen (p < 0.05, figure 1). The cumulative 5-year overall survival rate was 75% in the 1-MM HVG group, 50% in the 1-MM GVH group, 50% in the 1-MM bidirectional group, and 44% in the 8/8 matched group. Median survival of 1-MM HVG and 8/8 matched group didn't reach under analysis, and which is 62.2 months in 1-MM GVH, 30.9 months in 1-MM bidirectional group. The outcome of overall survival was more favorable in the 1-MM HVG group (Figure 2 and Figure 3), especially comparing with 1-MM bidirectional group (p=0.07), where there was no significant difference between 8/8-matched group and 1-MM GVH group or the 1-MM bidirectional group. Superior overall survival and relapse free survival was observed in 1-MM HVG group, although the differences were not statistically significant. Hyper-acute GVHD was slightly higher in 7/8 bidirectional group, while no significant difference was observed in acute and chronic GVHD among four groups. The primary causes of death were reviewed. 8/8 matched group had higher deaths attributed to disease relapse (26.3%), while 1-MM GVH group had more deaths attributed to GVHD (22.2%). Conclusion: Myeloabltive conditioning regimen is associated with more favorable outcomes of overall survival and relapse free survival. 1-MM HVG also tends to have superior overall survival and relapse free survival, although there is no statistical significance due to limited cases. Disclosures No relevant conflicts of interest to declare.

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