High levels of circulating CD34+ cells at autologous stem cell collection are associated with favourable prognosis in multiple myeloma

Raschle, Joëlle; Ratschiller, Daniel; Mans, Sarah; Mueller, Beatrice U.; Pabst, Thomas

doi:10.1038/bjc.2011.329

Cited by 17 publications

(11 citation statements)

References 27 publications

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“…Schulman et al [9] noted a 100-day mortality of 5.9% in the lower cell dose group versus 2.7% in the higher cell dose group. An improved outcome in PFS and OS patient with multiple myeloma with higher CD34 + cells mobilized has also been reported [18], although no such relationship was noted in patients with NHL [15]. Notably, in our study we observed inferior PFS and OS in patients receiving the lowest CD34 cell doses (<2 × 10 6 CD34 + cells/kg), which appeared to be associated with a trend toward higher 100-day nonrelapse mortality and risk of relapse.…”

Section: Discussionsupporting

confidence: 56%

Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors

Hyder

Goebel

Ervin

et al. 2018

Biology of Blood and Marrow Transplantation

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Tandem autologous stem cell transplantation (ASCT) improves long-term survival of platinum-refractory germ cell tumors (GCT) patients. Studies, predominantly in lymphoma, showed that CD34 cell doses > 5.0 × 10/kg/single transplant led to decreased resource utilization. Because most GCT patients have received prior cisplatin-based treatment, collecting >10 × 10 CD34 cells/kg is challenging. We analyzed the effect of CD34 cell dose on resource utilization and outcome in 131 GCT patients, median age 29.5 years (range, 16 to 58), undergoing tandem ASCT. Of 262 individual transplants performed, 120 were performed as inpatient and 142 as planned outpatient. Overall, median CD34 dose per transplant was 3.1 × 10/kg (range, 0.8 to 16.0), with no significant difference between inpatient and outpatient transplants. Patients were divided into quartiles based on the CD34 cell dose infused: Q1, 0.8 to 1.9 × 10/kg; Q2, 2.0 to 2.9 × 10/kg; Q3, 3.0 to 4.1 × 10/kg; and Q4, 4.2 to 16.0 × 10/kg. For all patients higher CD34 cell doses were associated with significantly shorter times to neutrophil (P <.001) and platelet recovery (P <.001). For inpatient transplants higher CD34 doses were significantly associated with shorter length of hospital stay (P <.001), fewer days of filgrastim (P <.001), i.v. antibiotic (P = .012) and antifungal (P = .03) usage; and fewer RBC (P = .001) and platelet units transfused (P <.001), resulting in overall lower cost of care (P< .001). Of the 142 planned outpatient transplants, 100 admissions were required for a median length of hospital stay of 7.0 days (range, 1 to 18). Although there was no significant difference in the rates of hospitalization between patients in different CD34 cell dose quartiles, a significant trend was observed for shorter hospitalization (P = .01) and fewer RBC (P = .002) and platelet (P = .005) transfusions with higher CD34 cell dose quartile. Patients receiving CD34 cell doses in the lowest dose quartile (Q1) had significantly worse progression-free survival and overall survival compared with patients receiving higher CD34 cell doses. Overall, resource utilization, including cost of care, is significantly reduced when patients receive higher CD34 cell doses, indicating greater efforts to improve peripheral blood stem cell collection in this population are needed.

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Section: Discussionsupporting

confidence: 56%

Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors

Hyder

Goebel

Ervin

et al. 2018

Biology of Blood and Marrow Transplantation

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“…Others and we have shown that high numbers of peripheral circulating CD34+ cells at PBSC collection are associated with a higher relapse risk, whereas delayed hematologic recovery after autologous HCT is associated with better PFS and OS [ 6 , 24 , 25 , 26 , 27 ]. Thus, a decreased mobilization potential after induction chemotherapy in AML patients may hamper a successful stem cell collection, but it indicates a favorable course of the disease most likely reflecting the effectiveness of the preceding chemotherapy against leukemic, and normal, hematopoietic stem cells [ 6 , 26 , 27 , 28 ]. This concept is in remarkable contrast to myeloma patients undergoing HDCT with autologous HCT [ 6 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Are Autologous Stem Cells More Difficult To Collect In Olmentioning

confidence: 99%

“…Thus, a decreased mobilization potential after induction chemotherapy in AML patients may hamper a successful stem cell collection, but it indicates a favorable course of the disease most likely reflecting the effectiveness of the preceding chemotherapy against leukemic, and normal, hematopoietic stem cells [ 6 , 26 , 27 , 28 ]. This concept is in remarkable contrast to myeloma patients undergoing HDCT with autologous HCT [ 6 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Are Autologous Stem Cells More Difficult To Collect In Olmentioning

confidence: 99%

Autologous Transplantation for Older Adults with AML

Mueller

Seipel

Bacher

et al. 2018

Cancers

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While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are common leading to poor long-term survival outcomes. Since autologous hematopoietic stem cell transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding graft-versus-host disease associated with allogeneic transplantation, it represents an option for consolidation treatment in selected older AML patients. However, prospective studies in older AML patients assessing the benefit of autologous HCT compared to chemotherapy consolidation or allogeneic transplantation are lacking. Consequently, clinicians face the dilemma that there is considerable ambiguity on the most appropriate consolidation treatment for older AML patients in CR1. This review highlights the possible role of autologous HCT for consolidation in older AML patients reaching CR1 after induction treatment.

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“…16 Other parameters obtained during treatment with favorable impact on relapse risk may include the decrease of the stem cell mobilization potential, delayed hematologic recovery after consolidation treatment, and low levels of transfusion-dependent iron load. [17][18][19] In this study, we assessed whether inter-individually differing kinetics of platelet recovery after induction chemotherapy may also confer relevant prognostic information. Thrombocytopenia is a common finding at diagnosis of AML, with surprisingly poor correlation to the degree of bone marrow infiltration.…”

Section: Introductionmentioning

confidence: 99%

Rebound Thrombocytosis after Induction Chemotherapy Is a Strong Biomarker for Favorable Outcome in AML Patients

Pabst¹,

Schnell

Bacher

et al. 2019

Blood

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Background: Whereas the molecular events underlying acute myeloid leukemia (AML) are increasingly identified, dynamics of hematologic suppression and recovery following induction chemotherapy remain enigmatic. In addition, thrombocytopenia at diagnosis is related to deregulated cytokine expression in specific leukemia subtypes rather than on the degree of bone marrow infiltration per se. Similarly, recovery of platelets after the first induction cycle among individual patients can vary from incomplete to excess recovery even if morphologic remission is achieved. In particular, excess platelet rebound (EPR) with values exceeding 500 G/L can be observed in some patients. However, this clinical observation of EPR is poorly understood so far, and its prognostic relevance is unknown. Methods: We analyzed platelet recovery after the first induction cycle in 291 consecutive AML patients receiving at least one cycle of intensive "3+7" based induction treatment. We defined excess platelet rebound (EPR) as a platelet increase above 500 G/L during hematologic recovery after the first induction cycle. Results: We observed EPR in 120 (41.2%) patients. EPR+ patients had lower platelets at diagnosis, higher marrow infiltration, more frequently NPM1 mutations, and were associated with ELN favorable risk. Absence of EPR correlated with complex karyotypes, ELN intermediate-I and adverse risk, and therapy-related AML. Overall survival was better in EPR+ patients than EPR- (median 125 versus 41 months; P=0.04), as was disease-free survival (Figure 1). By multivariate analysis, achievement of EPR+ was an independent parameter associated with favorable survival. Plasma thrombopoietin (TPO) levels at diagnosis indicated EPR+ (p<0.0001), while GATA-1, GATA-2 and MPL mRNA expression did not differ between EPR+ and EPR- patients. Finally, transcription factors blocking early megakaryopoiesis were upregulated in EPR- patients, while NFE2 involved in late megakaryocyte differentiation was increased in EPR+ patients. Conclusion: This study suggests that excess platelet rebound (EPR+) defined as platelets exceeding 500 G/L is a common event identified in AML patients after the first induction cycle. EPR+ was predominantly observed in ELN favorable risk AML, and it was associated with significantly better overall and disease-free survival as compared to EPR- patients. In addition, achievement of EPR+ represented an independent prognostic parameter for improved survival in a multivariate analysis, and may contribute to prognostic assessment in AML patients undergoing intensive treatment with intention to cure. Disclosures No relevant conflicts of interest to declare.

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High levels of circulating CD34+ cells at autologous stem cell collection are associated with favourable prognosis in multiple myeloma

Cited by 17 publications

References 27 publications

Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors

Low CD34+ Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors

Autologous Transplantation for Older Adults with AML

Rebound Thrombocytosis after Induction Chemotherapy Is a Strong Biomarker for Favorable Outcome in AML Patients

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