CFU-GEMM Infused Influences Immunologic Recovery in Children Older Than 7 years After Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4483-4483
Author(s):  
Katarzyna Drabko ◽  
Marta Choma ◽  
Agnieszka Zaucha-Prazmo ◽  
Beata Wojcik ◽  
Dorota Winnicka ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Helper Cells ◽  
Suppressor Cells ◽  
T Helper ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Group 2 ◽  
Graft Quality ◽  
T Suppressor Cells ◽  
Group 1

Abstract Abstract 4483 Introduction Reconstitution of immunity is considered as one of the most important factors predicting outcome after hematopoietic stem cell transplantation (HSCT). Age of the recipient as well as graft quality reflect on this process however this influence is not completely understood yet. In this study we aimed to evaluate the influence of graft quality on recovery of lymphocyte subpopulation. Patients and Methods The total number of 63 patients who underwent allogeneic transplantation in one center between May 2002 and November 2008, were included into the study. Median age of the patient was 8,6 (range 0.2-18) yrs. Patients were divided into 2 age groups: group 1 (n=26) children age 0,2-7 and group 2 (n=37) children >7 yrs. In all cases quality of graft were assessed by counting WBC, CD34 cells and CFU-GEMM. 45 patients (21 in group 1 and 24 in group 2) were available for evaluation of immune reconstitution: in those patients the absolute number of lymphocytes CD3/CD19 (B) cells, CD3/CD4 (T helper) cell, CD3/CD8 (T suppressor) cells and CD3/CD16+56 (NK) cells were measured 3 and 6 months after transplantation. Results Younger children (group 1) received higher median number of transplanted nucleated cells (4.9×108 vs 2.5×108, p=0.008), CD34 cells (5.6×106 vs 2.1×106, p=0.02) and CFU-GEMM (2.25×104 vs 1.17×104, p=0.01) than older ones (group 2). No differences were found in absolute values of B, T-helper, T-suppressor and NK cells at 3 and 6 months after transplantation (Table 1). In older children (group 2), but not in younger ones, the number of GFU-GEMM transplanted negatively correlated with number of T-suppressor cells 3 months post HSCT (p<0,05; r=-0,7) and positively with number of T-helper cells 6 moths after HSCT (p<0,05; r=0,73). Conclusions Number of CFU-GEMM infused influences immunologic recovery in children older than 7 years after HSCT. Graft quality correlates with number of T-suppressor cells and T-helper cells during first 6 months after HSCT and these changes may contribute to post transplant complications. Supported by grant MNiSW of Poland N407 117 35 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Incorporating hematopoietic stem-cell transplantation after second-line carfilzomib-lenalidomide-dexamethasone (KRd)

2020 ◽  
Vol 11 ◽  
pp. 204062072092104
Author(s):  
Ja Min Byun ◽  
Sung-Soo Yoon ◽  
Youngil Koh ◽  
Chang-Ki Min ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Benefit ◽  
Line Treatment ◽  
Second Line ◽  
Hematopoietic Stem ◽  
Group 2 ◽  
Group 1

Background: Traditionally believed to be an integral part of multiple myeloma (MM) treatment, the role of hematopoietic stem-cell transplantation (HSCT) is being challenged. As such, we sought to evaluate the impact of HSCT in the era of novel agents. Methods: A multicenter, retrospective, longitudinal cohort study was carried out between January 2016 and December 2018. A total of 55 patients who received VTD (bortezomib-thalidomide-dexamethasone) as first-line treatment and KRd (carfilzomib-lenalidomide-dexamethasone) as second-line treatment were analyzed for outcomes. Results: The enrolled patients were divided into Group 1, defined as those who continued KRd treatment until progression ( n = 41), versus Group 2, defined as those who underwent HSCT after a certain number of cycles of KRd ( n = 14). Both groups showed a generally favorable response to KRd, with overall response rate (ORR) of 87.9% and clinical benefit rate of 92.8% after a median of seven cycles in Group 1, and ORR 92.8% and clinical benefit rate 100% after median of five cycles in Group 2. However, significantly poorer progression-free survival (PFS) ( p = 0.004) was observed in Group 1 (median 12 months) compared with Group 2 (median not reached). Multivariate analyses identified HSCT after KRd as potential risk factors associated with PFS. Also, in Group 1, bortezomib refractoriness was associated with significantly shorter PFS compared with those who were responsive (median 12 months versus 14 months, respectively, p = 0.039). Conclusions: In conclusion, even with the advent of novel agents, HSCT still remains a valuable treatment modality with additive efficacy.

Effect of the Adminstration of Rituximab between Mobilization Chemotherapy and Leukapheresis on Stem Cell Collection Parameters: A Study of Fifty NHL Patients Mobilized Using Intermediate Dose Cyclophosphamide and Sequential GM-CSF and G-CSF.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2874-2874
Author(s):  
Asad Bashey ◽  
Lin Liu ◽  
Anita Ihasz ◽  
Ewa Carrier ◽  
Januario Castro ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Time Course ◽  
Cumulative Probability ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Group 2 ◽  
Stem Cell Collection ◽  
Intermediate Dose ◽  
Group 1

Abstract We have previously reported that intermediate dose cyclophosphamide followed by sequential GM-CSF and G-CSF (iCy/GM/G) provides efficient mobilization for patients undergoing autografting. Furthermore, the predictable time course of mobilization with this regimen obviates the need for weekend leukaphereses (Blood 2003: 957a). Recently, the addition of rituximab to mobilization regimens for B-cell NHL has been shown to be effective at depleting contaminating B-cells from the leukapheresis product. However, the effect of rituximab administered for in-vivo purging, on mobilization and stem cell collection parameters is unclear. We compared leukapheresis (LP) yield parameters, and the time course of stem cell mobilization in 23 consecutive B-cell NHL patients mobilized with iCy/GM/G plus rituximab (group 1) with 27 consecutive B-cell NHL patients mobilized with the same regimen without rituximab (group 2). The iCy/GM/G regimen consisted of cyclophosphamide 1.5g/m2 (d1), GM-CSF 500 mcg/d (d 3–7), G-CSF (d 8 until completion of LP) 600mcg/d for weight ≤80kg, 960 mcg for weight &gt; 80 kg. Rituxan was administered at 375mg/m2 as a single dose on d8. LP was begun on d 11 irrespective of WBC. D1 was usually a Friday in order to avoid weekend LP. Patients underwent up to 20 liter LP for ≤ 5 days (median =3, range 1–5 for both groups) with a target collection of &gt; 5 x 10e6 CD34+ cells/kg. The groups were well matched for median age, gender, number of prior chemotherapy regimens (median=2 for both groups), prior pelvic XRT and histological subtype of B-NHL (p=NS in all cases). The estimated (Kaplan-Meier) cumulative probability of achieving a target collection of 2 x 10e6 CD34+ cells/kg on d 1–5 was 0.43, 0.70, 0.78, 0.84, 0.84 respectively for group 1 and 0.22, 0.69, 0.77, 0.84, 0.84 respectively for group 2. The corresponding probabilites of achieving 5 x 10e6 CD34+ cells/kg on d 1–5 were 0.22, 0.39, 0.57, 0.57, 0.57 (group 1) and 0.11, 0.30, 0.46, 0.59, 0.59 (group 2) (p=NS Log-rank test). Percentage of CD34+ cells in the LP product (LP CD34%) was measured daily. Maximums LP CD34% was seen on LP d1 for both groups with a fall on subsequent days (p=NS between groups 1 and 2). Toxicities experienced were generally mild consisting mostly of bone pain and fevers and were similar in both gropups. No patient required admission for febrile neutropenia. The number of CD34+ cells infused were similar for both groups (median 5.9 vs.5.7 x10e6 CD 34+ cells/kg). Median time to reach ANC &gt; 500/mm3 and platelets &gt; 20,000/mm3 were identical between groups 1 and 2 (d11 and d 10 respectively). These data show that the addition of rituximab administered on d 8 to the iCy/GM/G regimen in patients with B-NHL does not impair the yield of CD34+ cells, or the tolerability of the regimen. Furthermore, the time course of the mobilization and therefore the predictbility of the collection is not compromised. Maximum cumulative yield of CD34+ cells is achieved within 4 days of LP with no patient benefitting from a fifth day of collection. The additional cost and inconvenience of weekend leukapheresis can be avoided in all cases using this regimen.

Influence of First-Line Regimens on the Outcomes of High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 931-931 ◽  
Author(s):  
Bimalangshu R. Dey ◽  
Benjamin Cox ◽  
A. Jo Chien ◽  
Martin Caron ◽  
Steven L. McAfee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Hematopoietic Stem ◽  
Group 2 ◽  
Group 1

Abstract Randomized trials that incorporated high-dose chemotherapy (HDC) plus autologous hematopoietic stem-cell transplantation (Au-HSCT) into the early treatment of patients with newly diagnosed multiple myeloma demonstrated superior overall and event-free survival (EFS) in patients 65 years of age or younger, who received Au-HSCT, as compared with patients who received conventional chemotherapy. Based on these encouraging results, Au-HSCT is recommended for patients with myeloma as part of their initial treatment, and today, myeloma is the most common indication for HSCT in the world. All patients in these trials received four to six months of conventional chemotherapy prior to HDC and Au-HSCT. In practice, however, both in the community as well as in academic hospitals, patients are undergoing Au-HSCT after being treated with various first-line regimens, including chemotherapeutics, high-dose dexamethasone (HDex), immunomodulatory drugs such as thalidomide and recently, proteasome inhibitors. In this retrospective study, we examined the impact of first-line therapy on the outcomes following Au-HSCT. Our objective was to compare two treatment groups - chemotherapy versus non-chemotherapy, prior to Au-HSCT - with respect to survival after Au-HSCT. Between 1997 and 2004, 37 previously untreated evaluable patients with myeloma, received either chemotherapy (group 1, n=25; vincristine, adriamycin and dexamethasone (VAD), n=24; melphalan and prednisone (MP), n=1) or non-chemotherapy regimens (group 2, n=12; HDex, n=9; thalidomide plus HDex, n=3), then received HDC followed by cyclophosphamide plus granulocyte colony stimulating factor-mobilized HSCT. The median age of patients in group 1 was 58 (range, 44–73) years and in group 2 was 55 (range, 41–67) years; 22 patients in group 1 (88%) and 10 patients in group 2 (83%) had stage III disease; the median times from diagnosis to HSCT were 6 (range, 5–16) and 8 (range, 5–25) months, respectively, in groups 1 and 2. The rates of complete and near-complete response were 44% in group 1 and 42% in group 2; the rates of partial responses were also similar: 48% and 42% respectively. The median duration of EFS was 31 (range, 7–89) months, and the median overall survival (OS) was 55 (range, 12–98) months in group 1, as compared with group 2 where EFS and OS were 21 (range, 12–40) and 31 (range, 16–76) months, respectively. The EFS at 3 years was 44% in group 1 and 25% in group 2, and OS at 5 years was 32% in group 1 and 8% in group 2 (statistically not significant). In conclusion, patients with newly diagnosed myeloma, when treated with chemotherapy prior to Au-HSCT, may have long-term overall and EFS advantages, as compared with patients who are treated with first-line non-chemotherapy regimens. The reasons for the longer duration of response in the chemotherapy group despite similar response rates in the two groups are unknown, but may be due to more effective suppression of residual disease or non-specific damage to the marrow microenvironment, which is necessary for the growth of myeloma cells. Although, the difference in survival outcomes following Au-HSCT between the two groups did not achieve statistical significance, our results raise an important question regarding the “adequacy” of different first-line regimens prior to Au-HSCT, and therefore, justify the need for prospective randomized studies to evaluate optimal pre-AuHSCT induction therapy.

Impact of Peripheral Blood Stem Cell Recruitment on Outcome of Single or Double Autologous Hematopoietic stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5221-5221
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Le ◽  
Anne-Sophie Michallet ◽  
Anne Thiebaut ◽  
Emmanuelle Tavernier ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Light Chains ◽  
Hematopoietic Stem ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Multiple myeloma remains one of the best indication for intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (autoT). Intensive therapy followed by autologous transplantation is superior to conventional chemotherapy and it was demonstrated that two autoT were superior to one except for patients in very good partial response or in complete response after the first autotransplant. Peripheral blood stem cells (PBSC) can be used as well as bone marrow as HSC source with the same efficacy but very few data have been reported regarding PBSC recruitment. The main goal of our work was to study the impact on overall and event-free survival (OS and EFS) of PBSC recruitment using either growth factors (GF) alone (steady state) or chemotherapy followed by GF. Secondly, we performed a multivariate analysis studying influence on OS and EFS of sex, age, lines of therapy, pretransplant status, TBI, PBSC recruitment and number of autoT. We have analyzed 193 PBSC autoT (1 autoT=160, 2 autoT=33) performed for 160 MM patients [81 males and 71 females, mean age: 55 years (39–71)]. At diagnosis, 88 patients presented a MM Ig G (70k and 18l), 28 Ig A (16k and 12l), 3 Ig D (1k and 2l), 21 light chains k and 13 light chains l, 3 non secreting and 4 with plasmocyte leukemias. According to Durie and Salmon classification 75% of patients were in stage III, 15% in stage II and 10% in progressive I. Before transplantation, patients have received 1 line of poly-chemotherapy (n=141), 2 lines (n=15) or 3 lines (n=4) and 154 were evaluated for the response with 11 complete remission, 113 partial remission and 30 stable or evolutive disease just before transplant. As HSC (n=189), patients received PBSC which were recruited by GF alone (n=105) or cyclophosphamide+GF (n= 84). Conditioning (n=189),consisted in melphalan and TBI (n=51), melphalan alone (n=132), melphalan associated to cyclophosphamide or busulfan (n=6). We divided the population into 4 groups : group 1 who received one autoT of PBSC recruited by GF (n=76), group 2 one autoT of PBSC recruited by chemotherapy+GF (n=50), group 3 two autoT of PBSC recruited by GF (n=16) and group 4 two autoT of PBSC recruited by chemotherapy+GF (n=17). The median follow-up (FU) of the 4 groups were different with shorter FU (group 3: 9.9 months, group 4: 13 months) for patients who received tandem autoT because of the recent character of this strategy as compared to a long term follow-up for patients who received only one transplant (group 1: 35months, group 2: 55.3 months). Probabilities of OS and EFS at 2 years were 76% (95%CI 67–87) and 60% (95%CI 49.5–73) for group 1, 77% (95%CI 65–90.5) and 70% (95%CI 57.5–85) for group 2, 87.5% (95%CI 73–100) and 72.9% (95%CI 49–100) for group 3, 100% and 66.7% (95%CI 36–100) for group 4. The difference was not significant because of follow-up differences between the 4 groups and small number of patients in groups 3 and 4. In addition, multivariate analysis did not show any significant influence of the different studied parameters on OS and EFS. Nevertheless, because of these interesting preliminary results, a longer follow-up is warranted for definitive conclusions.

Leukemic and Hematopoietic Stem Cells Compete for the Same Functional Marrow Niche in a MLL-AF9 Murine Leukemia Model

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4897-4897
Author(s):  
Ronan G. Desmond ◽  
Taha Bat ◽  
Olena Kamenyeva ◽  
Benjamin Mizukawa ◽  
James C. Mulloy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Murine Model ◽  
Leukemic Cells ◽  
Hematopoietic Stem ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Abstract 4897 Much is known regarding the location, cellular composition, signaling pathways, and functional role of the normal hematopoietic stem cell (HSC) niche in the bone marrow microenvironment. Microenvironmental cells including osteoblasts, other specialized mesenchymal cells, and vascular endothelial cells exert control over HSC self-renewal, differentiation, and engraftment. Niche occupancy appears to be competitive and limiting in terms of controlling the number of HSCs per organism. Leukemia stem cells (LSCs), through their inherent properties of quiescence and resistance to chemotherapeutic agents, are thought to be one of the principal mechanisms underlying disease relapse in patients. Much less is known regarding the interaction of LSCs and the marrow microenvironment. It is not clear whether LSCs localize to the same niches as HSCs, compete with HSCs for niche occupancy, or share dependence on niche signals, and whether those signals affect tumor responses to chemotherapy. Using a human pre-B ALL xenograft mouse model, Colmone et al (Science 2008) recently showed that leukemic cells may alter the normal microenvironment, resulting in initial homing of transplanted normal HSPCs in distinct atypical niches. Shiozawa et al (JCI 2011) showed that metastatic prostate cancer cells, a tumor type known to target bone, impeded HSC engraftment in a murine model, suggesting competition for the same niche. To investigate the relationship between HSC and LSC niche localization and functional occupancy, we used murine progenitor cells transduced with an MLL-AF9 vector expressing GFP in a murine syngeneic competitive transplantation model. MLL-AF9 cells are highly enriched for LSCs, particularly the c-kit+ compartment (Somervaille Cancer Cell 2006). We found that between approximately 21% and 24% of cells were c-kit+ by FACS in 2 separate experiments. In our model, mice transplanted with unsorted MLL-AF9 cells (1×107) died of AML with a latency of 11–14 days. We cotransplanted a fixed number of MLL-AF9-GFP cells (1×106) with increasing numbers of normal mouse whole bone marrow (WBM) cells, derived from dsRed transgenic mice to facilitate distinction from the GFP+ MLL-AF9 cells, into mice irradiated with 1000 rads: 1×105 [group 1], 1×106 [group 2], 1×107 [group 3], 5×107 [group 4]. Control groups received 1×105 and 1×106 normal WBM cells only. Survival was monitored daily. The control group receiving 1×105 cells only all died with median time to death of 16.5 days from lack of count recovery, those receiving 1×106 cells are still alive 35 days after transplant, indicating that 1×106 cells is adequate to rescue from irradiation. Mice were bled weekly until death and samples were analyzed by flow cytometry. Complete blood counts, blood smears, and splenic sections were obtained from these mice. As expected, there were no circulating blasts detected 7 days post transplant and all mice were healthy. However, 14 days after transplant the percentages of GFP+ leukemic cells detected in the blood were inversely proportional to the number of normal dsRed WBM cells transplanted (group 1 vs. group 2 vs. group 3 vs. group 4 mean percentage of GFP+ cells, 83.97 v 66.53 v 18.73 v 9.275 p< 0.0001). At day 15, mice from group 1, but not from groups 2 to 4, became moribund and were sacrificed. Spleens in this group were heavier than in those mice transplanted with 1×105 normal WBM cells alone and 2 out of 3 showed leucocytosis compared to leucopenia in all mice in the group transplanted with normal cells alone. When mice in the other groups had blood samples taken for analysis while moribund, GFP+ cells were greater than 80% suggesting that mice in group 1 died from complications relating to leukemic infiltration. Confocal microscopy confirmed the colocalization of normal HSPCs and MLL-AF9-GFP LSCs in the niche. Most interestingly, survival was proportional to the numbers of normal WBM cells transplanted, with a continuous delay in leukemic death proportional to the number of normal WBM cells cotransplanted with the same dose of MLL-AF9 cells (Figure 1). Hence, this murine model of leukemia suggests that normal and leukemic cells compete for the same functional niche, that manipulation of the niche could impact on response to anti-leukemic therapies, and that cell dose in the context of stem cell transplantation for leukemia may have an impact on outcome via niche competition. Figure 1 Figure 1. Disclosures: No relevant conflicts of interest to declare.

Evaluation of Three Different Cyclosporine-Based Graft Versus Host Disease (GVHD) Prophylaxis Regimens Following Nonmyeloablative Hematopoietic Stem Cell Transplantation (NST).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1236-1236 ◽  
Author(s):  
Ramaprasad Srinivasan ◽  
Nancy Geller ◽  
Sakti Chakrabarti ◽  
Igor Espinoza-Delgado ◽  
Teresa Donohue ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Malignant Diseases ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
High Incidence ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Acute GVHD is a major contributor to morbidity and mortality following NST. A high incidence of grades II–IV GVHD occurs when cyclosporine A (CSA) alone is used as prophylaxis. Consequently, we investigated the effect of combining either mycophenolate mofetil (MMF) or methotrexate (MTX) with CSA on the incidence and severity of acute GVHD. Between 11/97 and 07/04, 185 consecutive patients (solid tumors n=116, hematologic malignancies n=48, non-malignant hematologic disorders n=21) underwent nonmyeloablative conditioning with fludarabine (125mg/m2) and cyclophosphamide (120mg/kg), followed by a G-CSF mobilized peripheral blood hematopoietic stem cell transplant from an HLA identical (n=177: 96%) or 5/6 antigen-matched (n=8: 4%) related donor. Twenty-four patients with a history of heavy RBC transfusions or those receiving a 5/6 HLA-matched transplant had anti-thymocyte globulin (40mg/kg/d x 4 days) added to their conditioning regimen. The initial cohort of patients (Group 1, n=66), received CSA alone (dose adjusted to maintain therapeutic serum levels) as GVHD prophylaxis. Due to the high incidence of severe acute GVHD in this group subsequent patients received CSA with either MMF (1 gram po bid; Group 2, n=82) or MTX (5mg/m2 days +1, +3, +6; Group 3, n=37). In all three groups, decisions regarding discontinuation of immunosuppression were based on the degree of donor T cell chimerism, presence of GVHD, and disease status in those with malignant diseases. In the absence of grade II–IV GVHD and disease progression, CSA (+/− MMF) was tapered slowly beginning on day +60. Baseline characteristics of patients in the three groups were compared using the Wilcoxon test for continuous variables and chi-squared tests for discrete variables. The three groups did not differ significantly in terms of age, sex, sex mismatch (female into male) and CD34 cell dose. Median follow-up in groups 1, 2 and 3 was 1901 days, 1248 days and 346 days respectively. The cumulative incidence of grades II–IV GVHD in these three groups was 56% (95% CI 44%–68%), 59% (95% CI, 48%–70%), and 34% (95% CI 18%–50%, p=0.11) respectively. The cumulative incidence of grades III–IV GVHD (30% vs. 34% vs. 16%, p=0.2) and the incidence of chronic GVHD (46% vs. 57% vs. 50%, p=0.49) were also similar in the three groups. Transplant related mortality was 15% (95% CI, 6%–24%) in group 1, 12% (95% CI, 5%–19%) in group 2 and 5% (95% CI, 0%–13%) in group 3 patients (p=0.44). The cumulative incidence of death from acute GVHD was 9% (95% CI, 0%–16%) and 2% (95% CI, 0–5%) respectively in groups 1 and 2, while no deaths from acute GVHD occurred in group 3. Overall survival in the three groups did not differ significantly (log-rank test, p=0.48), with medians 244 days (95% CI 196–402), 486 days (95% CI 306–620) and 438 days, (95% CI 210–662) respectively. The impact of adding MMF or MTX to CSA on disease-specific outcome in patients with malignant diseases was not assessed. Conclusion: There was a trend towards a lower incidence of grades II–IV GVHD in group 3 patients. However, despite the addition of either MMF or MTX to CSA, severe grade III–IV acute GVHD remains a major morbidity complicating NST. Additional strategies aimed at preventing GVHD and optimizing the management of established GVHD are needed to improve outcome following this approach.

Imaging the Differential Engraftment of GFP-Expressing Spleen and Bone Marrow Cells in Various Organs after Reduced-Intensity Stem Cell Transplantation in Mice Model.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3228-3228
Author(s):  
Yuji Heike ◽  
Zhijian Yang ◽  
Huaiyu Ma ◽  
Robert Hoffmann ◽  
Yuriko Morita ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Pelvic Bone ◽  
Donor Cells ◽  
Cd34 Cells ◽  
Group 2 ◽  
Reduced Intensity ◽  
Group 1

Abstract [Background] Reduced-intensity allogeneic stem cell transplantation is of critical importance in the treatment of hematological malignancies. The object of this experiment is to establish fludrabine-based reduced-intensity allogeneic stem cell transplantation model using donor cells labeled with GFP and image the engraftment process of donor cells in various organs. [Materials and Methods] GFP transgenic C57/BL6 mice (GFP-Tgm) were used as donors and C57/BL6 × DBA F1 mice (BDF1) were used as recipients. Recipient mice were pretreated with fludarabine (Flu) 150 mg/kg/day × 6 days i.p. and cyclophosphamide (CPA) 150 mg/kg/day × 2 days i.p. On day 0, 107 GFP splenocytes (Group 1) and GFP bone marrow cells (Group 2) were injected in the tail vein. Whole body and intravital imaging were used to visualize the migration of GFP-Tgm cells into various organs including the brain, femur, intestine, liver, lung, ovary, pelvic bone, ribs, skin, skull, spine, spleen and uterus on days-7 and -14. The macro images were obtained with the Olympus OV100 Small Animal Imaging System. GFP-Tgm cell migration, particularly CD34+ cells in the various organs was also analyzed by flow cytometry (FACS) using APC-labeled anti-CD34 monoclonal antibodies. [Results and Discussion] On day-7, the migration of donor GFP-Tgm cells in peripheral lymph nodes, intestine, lung, ovary, skin and uterus were detected in both groups. Migration of GFP-Tgm cells in the femur, pelvic bone, ribs and skull were clearly detected in Group 2, but not in Group 1. On day-14 GFP donor cells were imaged in the lung, ovary, skin and uterus both groups. However, GFP-Tgm cells were no longer imaged in the intestine in Group 2 except in Payer patches. In both groups the GFP-Tgm cells were strongly detected in the femur, pelvic bone, skull and spine on day-14. We also analyzed the migration of CD34+ GFP-Tgm cells by FACS analysis. On day-14, the percentage of GFP-Tgm cells in the bone marrow and spleen was, respectively, 14% and 53% in Group 1, and 10% and 13% in Group 2. The percentage of CD34+ GFP-Tgm cells among total CD34+ cells in the bone marrow was 10% in Group 1 and 14% in Group 2, and in the spleen was 24% and 19%, respectively. Those results suggested that in this model, donor bone marrow and spleen cells, but not purified CD34+ cells, have different engraftment kinetics in various organs including the intestine, which is a target organ for graft-versus host disease. These results clearly suggest that caution should be paid to evaluate engraftment kinetics of infused cells, at least in mice model.

scholarly journals Effect of the Amount of Autologous Hematopoietic Stem Cells on Survival and Engraftment in Multiple Myeloma

2021 ◽  
Keyword(s):  
Multiple Myeloma ◽  
Disease Status ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Statistical Population ◽  
Cd34 Cells ◽  
Training And Research ◽  
Group 2 ◽  
High Dose Melphalan ◽  
Group 1

Background: Autologous stem cell transplantation (ASCT) is currently a gold standard treatment for eligible multiple myeloma (MM) patients. The recommended dose of CD34+ hematopoietic progenitor cells (HPCs) for adequate engraftment is above 2 × 106 cells/kg. Objectives: This study aimed to evaluate the relationship between the number of CD34+ HPCs and the survival in MM patients who underwent ASCT in the Hematology Department of Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey. Materials and Methods: The statistical population of this consisted of 200 MM patients who underwent ASCT within 2009-2019. The clinical characteristics of the patients, disease status pre-SCT, number of infused CD34+ cells, neutrophil, and platelet engraftment days were recorded. The patients were divided into two groups, based on whether the re-infused CD34+ HPCs dose was < 5 × 106 cells/kg (Group 1) or ≥ 5 × 106 cells/kg (Group 2). The groups were compared in terms of engraftment and overall survival (OS) times. Results: A total of 200 patients were included in our study. Group 1 (n=125) included patients with < 5 × 106 cells/kg CD34+ HPC re-infusion, and Group 2 (n=75) consisted of patients with ≥ 5 × 106cells/kg CD34+ HPC re-infusion. The patients’ median age scores in Group 1 and Group 2 were 57 (25-71) and 56 (33-72) years, respectively. The median follow-up period was 33 months (6-130). The median OS of all patients was 71 months (95% confidence interval, 59.1-82.9). The median neutrophil and platelet engraftment times were similar between the groups (P=0.4 and P=0.4, respectively). In both groups, the median OS time was 71 months (P=0.8), which was similar. Conclusion: The greater number of CD34+ HPCs re-infusion for ASCT after high dose melphalan chemotherapy in MM patients did not affect platelet and neutrophil engraftment time and OS; therefore, this amount of reinfusion was not required.

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