Median Number Of CD34 Research Articles

Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers

OBJECTIVE:To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers.METHODS:Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro.RESULTS:The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion.CONCLUSION:The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

Mobilization of Hematopoietic Stem Cells with Lenograstim in Healthy Donors: Efficacy and Safety Analysis According to Donor Age

We reviewed and analyzed safety and efficacy data after mobilization with granulocyte colony-stimulating factor (G-CSF) according to healthy donor's (HDs) age as follows: <50 years (HDs-1, n = 161), aged 50 to 59 years (HDs-2, n = 62), and ≥60 years or over (HDs-3, n = 23). Two hundred forty-six HDs were evaluated, and their characteristics were well balanced among age groups: most were male, siblings, and HLA matched. According to age group, the median numbers of CD34+ cells in the peripheral blood for HDs-1, HDs-2, and HDs-3 were, respectively, 44.5, 34.5, and 26 (HDs-1 versus HDs-2, P = .002; HDs-1 versus HDs-3, P = .036; HDs-2 versus HDs-3, P = n.s.) at day 4 and 65.5, 58, and 46 (HDs-1 versus HDs-2, P = .039; HDs-1 versus HDs-3, P = .002; HDs-2 versus HDs-3, P = n.s.) at day 5. With a median apheresis session of 1, the number of CD34+ cells/kg recipient body weight collected was not significantly different (6.4 in HDs-1, 6.0 in HDs-2, and 5.7 in HDs-3, P = n.s.). Short- and long-term safety did not differ among age groups. Bone pain was reported as the most frequent short-term adverse event (76.5%). After a median follow-up of 7.8 years, the observed rate of solid tumors, hematological malignancies, and cardiovascular and autoimmune events was similar to the expected incidence for these diseases in Western countries. These results show that G-CSF is effective in the mobilization of older HDs. Moreover, our data contribute to the growing body of evidence in support of the long-term safety of G-CSF for allogeneic donor stem cell mobilization also for elderly HDs.

Efficacy of vinorelbine plus G-CSF for CD34+ hematopoietic progenitor cell mobilization in patients with multiple myeloma

We aimed to assess the efficacy of vinorelbine plus G-CSF for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma and to identify adverse risk factors for successful mobilization. Vinorelbine 35 mg/m(2) was administered intravenously on day 1 in an outpatient setting. Filgrastim 5 μg per kg body weight (BW) was given twice daily subcutaneously from day 4 on until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and performed for a maximum of three consecutive days until at least 4x10(6) CD34+ cells per kg BW were collected. Overall, 223 patients were mobilized and 221 (99%) patients proceeded to leukapheresis. Three (1.5%) patients required an unscheduled hospitalization after chemo-mobilization due to neutropenic fever and renal failure (n=1), severe bone pain (n=1), and abdominal pain with constipation (n=1). In 211 (95%) patients the leukaphereses were started as planned at day 8, while in 8 (3%) patients the procedure had to be postponed to day 9 and in two (1%) patients to day 10. In the great majority of patients (77%) the predefined amount of HPC could be collected with one leukapheresis. Fourty-four (20%) patients needed a second leukapheresis, while only 6 (3%) patients required a third leukapheresis procedure. The median number of CD34+ cells collected was 6.56x10(6) (range, 0.18-25.9x10(6)) per kg BW at the first day of leukapheresis and 7.65x10(6) (range, 0.18-25.9x10(6)) per kg BW in total. HPC collection was successful in 212 (95%) patients after a maximum of three leukaphereses. Patient age (p=0.02) and prior exposition to lenalidomide (p<0.001) were independent risk factors for a lower HPC amount collected in multiple regression analysis. Vinorelbine plus G-CSF enables a very reliable prediction of the timing of leukapheresis and results in successful HPC collection in 95% of the patients.

Serem Ferritin Was the Only Prognostic Factor for Disease Free Survival in MDS Patients after Allo-HSCT: A Single Centre Study

▪Introduction: Myelodysplastic syndrome (MDS) represents a heterogeneous group of hematopoietic stem cell disorders characterized by single-lineage or multi-lineage cytopenias and a risk of progression to acute myeloid leukemia (AML). Despite the development of new drugs, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potential curative therapy. We have a retrospective analysis of the efficacy and security of the allo-HSCT therapy for MDS in our singal centre.Method: Between June1999 and March 2012, 39 MDS patients with a median age of 32 years (range, 12-52) were transplanted with a matched related donor (n=10), unrelated donor (n=20) or haploidentical donor (n=9) in our centre. Of the patients, 62% were male; 44% had intermediate-1 risk, 13% intermediate-2 risk and 43% poor risk cytogenetics by the International Prognostic Scoring System criteria. The cell source was bone marrow (BM) in 36%, peripheral blood (PB) in 59% and BM+PB in 5%. 51% patients had received chemotherapy prior HSCT. Conditioning regimens were BUCY or BUCY plus ATG for matched related HSCT and unrelated transplants, AraC+BuCy+ATG+MeCCNU for haploidentical transplants. The median number of CD34+ cells/kg infusion was 5.52×106(range, 0.8×106-10.38×106).Graft-versus-host disease prophylaxis was employed by cyclosporine A (CsA), mycophenolate mofetil (MMF) and short-term methotrexate (MTX). 25 patients received serum ferritin measurement berore HSCT. The mediun level of serum ferritin was 1100ng/ml (range, 456-2318).Result: The median follow-up was 27 months(range,1.5-154). The 3-year disease free survival(DFS) was 60.8%. Transplant related mortality(TRM) was assessed at 37% on the whole cohort. 5% has no engraftment for a total of 2 patients. A neutrophil count of >0.5 × 109/L was achieved at a median of 12 days (range, 9–24 days) and a platelet count of >20 × 109/L within 14 days (9–49 days) post-transplant. Acute GVDH grade 1-2 was documented in 49%, grade 3-4 in 5% and no GVDH in 46%. Chronic GVHD could be identified in 27 patients (69%), 5 of whom had extensive disease, while the other 22 had limited disease. Overall 14 patients (36%) died. Causes of death were Infection 57%,GVDH 8%, haemorrhage 14%, engraft failure 14% and “other causes” 7%. Only one patients died because of relapse of the disease.DFS according to donor source (matched related donor 87.5%, unrelated donor 51.6% and haploidentical donor 55.6%) was not significant (p =0.22 ). Likewise no significant difference was found on DFS among BM 57%, PB 66.4% and BM+PB 50% (p =0.65). A similar DFS was seen in different risk categories (56.7% in intermediate, 66.7% in high-risk; p=0.51). No difference was seen in DFS according to the CD34+ cell number and whether received chemotherapy prior to HSCT. Only the elevated serum ferritin is associated with inferior DFS after HSCT(p =0.018 ). DisclosuresNo relevant conflicts of interest to declare.

Lower Leukocytosis with Biosimilar Compared with Originator G-CSF during Autologous Stem Cell Mobilization after Chemotherapy in Lymphoma and Multiple Myeloma Patients. a Pharmacovigilance Study of “Rete Ematologica Lombarda” (FARMA-REL)

BACKGROUNDBased on therapeutic equivalence extrapolated from originator, the use of biosimilar Granulocyte-Colony Stimulating Factor (G-CSF) in the context of stem cell harvest was approved by the European Medicines Agency (EMA), however “ad hoc” studies are limited. AIMSTo assess the efficacy and safety profile of biosimilar compared with originator G-CSF on PBSC autologous mobilization in association with chemotherapy (CT) in lymphoma (LY) and multiple myeloma (MM) patients (pts) treated in the Hematology Units of “Rete Ematologica Lombarda” (REL). PATIENTS AND METHODSData retrospectively collected from consecutive pts with Hodgkin disease (HD), non-Hodgkin LY (NHL) and MM undergoing PBSC harvest after CT with biosimilar filgrastim between July 2012 and December 2013 (LY) or June 2014 (MM), were compared with a historical control group treated with originator G-CSF. Biosimilar G-CSF was used at doses ranging from 5 (MM and lymphoma HIV-negative) to 10 mcg/kg/d (lymphoma HIV-positive) subcutaneously, starting from the day after the end of CT until the end of leukapheresis. The Shapiro-Wilk test was used to assess normality of data: p-values were derived from chi-square test for categorical data and from Mann–Whitney U-test for continuous data. RESULTSOne hundred-five leukapheresis from 96 consecutive pts including 3 HD, 51 NHL (46 HIV-negative and 5 HIV-positive) and 42 MM cases were analyzed. Median age was 53 yrs (19-65) among LY and 63 (43-72) among MM pts. Thirty-two/54 (59 %) and 19/42 (45 %) cases were male, respectively. Mobilization was planned as part of first line CT in 65% of LY pts; only one case was mobilized during 3rd line CT. Forty-five LY cases (47 %) had been previously treated with alkylating drugs (47 %), three (3 %) with fludarabine-containing regimens. All MM pts mobilized after first line CT.Mobilization started a median of 13 (range 10-21) and 10 (range 10-18) days after CT for LY and MM, respectively; it was completed in a median of one procedure (range: LY 1-4, MM 1-3). Median number of CD34+ cells collected was: 9,1 (range 3,0-47) and 7,8 (range 4,1-12,9) x 106/Kg/pt in LY and MM pts, respectively. Planned end-point was reached in all MM cases and all but 2 LY cases (3 %).Biosimilar G-CSF use was well tolerated in both LY and MM pts: mild bone pain (WHO grade 1-2) was frequently reported (LY: 16/54, 23 %; MM: 16/42, 38 %); two LY pts needed treatment with acetaminophen for headache (1) and bone pain (1), both WHO grade 3.Data were compared with a historical control group of 58 LY pts (HD 10, NHL 45, NHL-HIV 3) and 32 MM pts mobilized with originator G-CSF (filgrastim or lenograstim)(Table): while MM cohorts are similar, LY cohorts differed for a higher frequency of mobilization with high-dose cyclophosphamide (2/54, 4 % vs. 14/58, 24 %, p<0.001) and a slight prevalence of HD cases (3/54, 5 % vs. 10/58, 17%, p= 0.053) only. Median number of procedures, CD34+ count peak and CD34+ collected were similar in both groups; however a difference in median WBC count peak during leukapheresis was documented in both cohort, statistically significant in LY, even if treated without cyclophosphamide.CONCLUSION. We confirm efficacy and safety of biosimilar filgrastim for autologous PBSC mobilization in LY and MM pts. Noteworthy, biosimilar seems to be more selective on CD34+ cells compared with originator G-CSF, inducing efficient CD34+ cells mobilization with lower leukocytosis. This result, confirmed in both LY and MM populations, needs to be proved in larger studies and can play a major role in the setting of voluntary donors. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Can Allo-HSCT Improve the Poor Clinical Outcome of the “Internal Tandem Duplication” of the FLT3 Gene?

AML patients (pts) with a normal chromosome pattern and the “Internal Tandem Duplication” (ITD) of the FLT3 gene have an overall and event-free survival (OS, EFS) inferior than those of pts with a FLT3 “wild-type” gene because of a higher relapse risk, are placed in the intermediate-1 prognostic category, and when in complete remission (CR) are candidates to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the role of allo-HSCT in ITD+ pts is still debated and a recent retrospective analysis has stated that FLT3/ITD adversely affected allo-HSCT outcome in the same direction as it does after chemotherapy.Thus, the present study was aimed to compare the OS, EFS and relapse risk of pts submitted to allo-HSCT in first CR or in initial relapse, defined by a 5-10% bone marrow blast cell percentage, with those of pts submitted to chemotherapy alone.The study cohort consisted of 54 chromosomally normal, ITD+ consecutive non-M3 AML pts who were included in 168 AML pts aged 18-66 years who came to our observation in the period January 2007-December 2013. At diagnosis median age was 48.6 years (range 18-66), 25 pts were males and 29 females. Median follow-up was 16.2 months (0.4-68.8): median follow-up for responsive pts was 7.15 months (range 0.26-27.6), for relapsed pts was 18.1 (range 1.9-68.8) and for transplanted pts was 9.1 months (range 2.9-26.8). All pts received the same induction treatment that consisted of standard Idarubicine+Ara-c “3+7” followed by two consolidation courses with high-dose Ara-c. Those who failed induction received other treatment schedules among which Fludarabine+Ara-c+Idarubicine was the most common. At the end of consolidation 38 pts were in first CR, achieved after 3+7 in 27 pts and after a second different course in 11. Sixteen pts had a resistant disease. After a median time of five months (range 1-21) 21/38 pts (55.2%) relapsed. All received a re-induction and 8/21 (38.1%) attained a second CR. Allo-HSCT was performed in a total of 23 pts: 12 first CRs, 6 second CRs and 5 initial relapses. The donor was a sibling in 7 pts, an unrelated donor in 13 and an haplo-identical donor in 3; the HSC source was the marrow in 6 pts, the peripheral blood in 16 and the cord blood (CB) in one. The Conditioning regimen was myeloblative (mainly Busulfan+Fludarabine) in 21 and non-myeloblative in 2; GvHD prophylaxis consisted of Cyclosporine A, steroids and methotrexate “short course”. The median number of CD34+ cells infused was 5.14x106/kg (1.3-12.7). All pts except that who received CB engrafted after a median time of 15 days (12-28); 21 were complete chimeras, two partial chimeras. Thirteen pts developed acute GvHD (grade I in 3 pts, grade II in 5, grade III in 2 and grade IV in 3) which totally/partially recovered after high dose steroids along with different immunosuppressive drugs in 4 and 9 pts respectively. Eleven pts developed a chronic GvHD which was the evolution of an aGvHD in 9, targeted different organs, was stable in 3 pts and completely/partially recovered in 4 and 2 pts respectively. Post-transplant relapse occurred in 3/12 first CRs, in none second CRs and in 3/5 initial relapse. The estimated response rate for CR pts submitted to allo-HSCT was 422.1 (95% CI: 262.4-679.1) versus 64.6 (95% CI: 40.7-102.6) for those submitted to chemotherapy alone with a median survival time of 7.2 months (range 5.3-8.8) versus not reached (1.9-not available); on univariable Cox model the HR of allo-HSCT pts was 37.9 (95% CI: 9.4-152.0) with p=0.0000. The estimated relapse rate for CR pts submitted to allo-HSCT was 8.6 (95% CI: 2.1-34.4) versus 44.3 (95% CI: 25.7-76.3) for those submitted to chemotherapy alone with a median survival time not reached (range not available) versus 13.2 (7.2-not available); on univariable Cox model the HR of allo-HSCT pts was 0.5 (95% CI: 0.2-1.1) with p=0.06. The estimated death rate for CR pts submitted to allo-HSCT was 28.7 (95% CI: 13.7-60.4) versus 49.7 (95% CI: 32.1-77.1) for those submitted to chemotherapy alone with a median survival time of 18.3 months (range 14.2-not available) versus 12.2 (8.8-18.9); on univariable Cox model the HR for allo-HSCT pts was 0.48 (95% CI: 0.2-1.1) with p=0.09.In conclusion, our series suggests that in ITD+ pts allo-HSCT significantly strengthens CR in pts who had already responded to conventional chemotherapy, but it presents only a trend towards significance when its superiority to prevent relapse was considered. DisclosuresCastagnola:Gilead Sciences: Research Funding.

Intrabone Injection of T-Cell Depleted Peripheral Blood Stem Cells from HLA-Haploidentical Donors to Reduce the Risk of Graft Rejection in Children

▪Background. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective treatment option for patients with malignant and non-malignant hematologic disorders lacking an HLA-compatible donor. Strategies for T-cell depletion (TCD) of the graft, such as positive selection of CD34+ cells, offer the potential to prevent acute and chronic graft-versus-host disease (GVHD). The risk of graft rejection associated with the extensive depletion of both T lymphocytes and accessory cells can be overcome by infusing a very high number (megadose) of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) (exceeding 10x106/kg recipient body weight) to overcome the HLA barrier (Aversa F. et al. Blood 1994). Moreover, the infusion of a megadose of CD34+ cells (higher than 20x106/kg and 12.4x106/kg, respectively) has been shown to result in faster immunological recovery and improved leukemia-free survival probability in children (Handgretinger R. et al. Bone Marrow Transplant 2001; Klingebiel T. et al. Blood 2010).Nevertheless, in the case of donors considered “poor mobilizers” (10-30% of cases), the threshold dose of CD34+ cells needed to ensure the inoculum of a megadose of stem cells might not be achieved. In the setting of cord blood (CB) transplantation, one of the strategies aimed at overcoming the problem of low cellularity is represented by the intrabone injection of CB stem cells, with good engraftment rates even in adult patients. We explored the same strategy in the context of T-cell depleted haplo-HSCT and low graft cellularity due to poor donor mobilization, ensuing in inadequate dose of CD34+cells available after positive selection TCD.Patients and methods. From September 2009 to April 2013, 11 pediatric patients affected by malignant or non-malignant hematological disorders (5 acute lymphoblastic leukemias, 1 acute myeloid leukemia, 1 myelodysplastic syndrome, 2 dyskeratosis congenita, 1 Fanconi anemia) received a T-cell depleted CD34+positively selected PBSC allograft from an HLA-haploidentical related donor.Due to the failure to achieve a target cell dose higher than 12x106 purified CD34+ cells/kg, part of the stem cell inoculum was infused as intrabone injection. The procedure was carried out at the patient bedside by multiple intrabone injections in the superior-posterior iliac crests under sedoanalgesia, as previously described (Frassoni F. et al. Lancet Oncol 2008). The median dose of CD34+ cells infused was 9x106/kg (range, 5-12) while the median number of CD3+ lymphocytes was 0.7x104/kg recipient body weight (range, 0.3-11). About one third of the stem cell inoculum, corresponding to a total volume of 20-40 ml, was given intrabone, while the remaining stem cell portion was infused intravenously.Results.No complication occurred during, or immediately after, the intrabone injection. Nine out of the 11 patients achieved a complete donor engraftment, while graft rejection occurred in 2 patients. The median time for neutrophil engraftment was 13.5 days (range, 12-20), while the median time for platelet recovery was 14 days (range, 13-24). One patient developed grade II acute GVHD and only 1 case of limited chronic GVHD was observed. No transplant-related deaths were observed.Conclusions. Our data suggest that, in the haplo-HSCT setting, the intrabone injection of positively selected CD34+ cells, can be safely used in cases of low graft cellularity due to poor donor mobilization, with the aim of minimizing the risk of graft rejection or poor engraftment. Our preliminary data need to be confirmed in larger series of patients and compared with those obtained with conventional intravenous administration of comparable dose of CD34+ cells. DisclosuresNo relevant conflicts of interest to declare.

A Randomized Comparison of Low-Dose Cyclophosphamide + G-CSF Versus G-CSF Alone Mobilization after Lenalidomide-Bortezomib-Dexamethasone (RVD) Induction in Multiple Myeloma

Introduction Autologous stem cell transplantation (ASCT) is the standard treatment in multiple myeloma (MM) for eligible patients below 70 years of age. The main mobilization treatment in Europe consists of combination of cyclophosphamide (CY) and G-CSF. It is questionable if CY is useful in mobilization. CY as an alkylating agent might also have some negative long-term effects. Bortezomib seems not to have negative impact on autologous stem cell harvesting, but prolonged use of lenalidomide might hamper mobilization. There are only a few studies regarding autologous stem cell mobilization after RVD induction. We designed this randomized study as a substudy of the Finnish Myeloma Group Study (NCT01790737) to compare the results of CY+G-CSF versus G-CSF mobilization in autologous stem cell harvesting. The primary endpoint is the percentage of patients reaching ≥ 3 x 106/kg CD34+ cells (or ≥ 6 x 106/kg for two transplants), with ≤ 2 apheresis after low-dose CY+G-CSF vs. G-CSF mobilization. Secondary endpoints are need for plerixafor, graft cellular composition and engraftment after ASCT. Patients and methods This phase 2 study will include 80 patients below 70 years of age with symptomatic MM and eligible for ASCT. At registration the patients are randomized equally to arm A) CY 2 g/m2 + G-CSF 5 μg/kg or arm B) G-CSF 10 μg/kg. Before mobilization three RVD induction cycles are given. Each 3-week RVD cycle includes lenalidomide 25 mg daily on days 1−14, bortezomib 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, and dexamethasone 160 mg/cycle. By this schedule the first harvest is estimated to be on day +10 in CY + G-CSF and on day +5 in G-CSF group. Apheresis will start with blood CD34+ level >10 x 106/l. The target cell yields for one and two grafts are ≥ 3 and ≥ 6 x 106 CD34+ cells/kg, respectively, and the minimum for one graft ≥ 2 x 106/kg. Plerixafor is given if B-CD34+ cell count is less than 10 x 106/l on days +10 or +5, respectively, or if the first apheresis product contains 0.5 x 109/l, and unsupported platelets > 20 x 109/l. Results Fifty-six patients have been included, and the mobilization data for the first 37 patients are available for analysis. The primary endpoint was reached in 90% of the patients (18/20) in arm A and in 82% (14/17) in arm B (p=NS). The median number of apheresis to reach the goal in arms A and B is one (1-3) and two (1−3), respectively (p=0.03). The median number of harvested cells in the two arms is 6.2 (2.2−12.1) and 4.8 (2.9−7.6) x 106/kg, respectively (p The median number of CD34+ cells transplanted, was 4.1 (2.2−7.3) and 3.2 (2.3−4.7) x 106/kg in arms A and B, respectively (p=0.01). In arm A the median neutrophil engraftment was on day +14 (9−28) (16 patients) and in arm B on day +15 (11−25) (15 patients) (p=0.68). The median platelet engraftment days were +13 (8−22) and +11 (8−21) in arms A and B, respectively (p=0.67). At ASCT the response rates in arm A were ≥ VGPR 65% (13/20), PR 25% (5/20), and 10% (2/20) were progressing, and the respective rates for arm B were 70% (12/17), 18% (3/17),and 12 % (2/17). Conclusions Preliminary results of this randomized mobilization substudy with a limited number of patients show no clinically significant differences between the number of harvested CD34+ autologous stem cells. However, in CY+G-CSF group the CD34+ cell target was reached by less aphereses. After short induction course of RVD it seems possible to harvest also for two autografts with G-CSF only mobilization. However, when compared to historical data the CD34+ cell counts in blood and grafts were lower than after bortezomib + dexamethasone induction, and also neutrophil engraftment seemed to be slower after lenalidomide-based induction therapy. We conclude that CY can be omitted in the mobilization regimen for MM patients who have responded to short course of RVD. Disclosures Silvennoinen:Janssen-Cilag: Research Funding; Celgene: Research Funding; Janssen-Cilag: Honoraria; Sanofi: Honoraria; Celgene: Honoraria. Porkka:BMS: Honoraria; BMS: Research Funding; Novartis: Honoraria; Novartis: Research Funding; Pfizer: Research Funding.

Hypercvad Induction Chemotherapy Is Associated with Higher Rates of Stem Cell Mobilization Failure in Mantle Cell Lymphoma ( MCL)

Background: MCL patients deemed fit for high dose regimens undergo induction therapy with rituximab and chemotherapy (HyperCVAD/CHOP/bendamustine) followed by consolidation with ASCT (autologous stem cell transplantation). R-HyperCVAD is a dose intense regimen with high response rates for MCL when used in the upfront setting (ORR 97%; CR 38%; Romaquera JE, JCO 2005). R-bendamustine and R-CHOP are contemporary regimens with similar efficacy (ORR 85-93%; Rummel MJ, Lancet 2013). In a recent randomized phase II trial (SWOG 1106) accrual to the HyperCVAD arm was stopped due to higher than expected rates of peripheral blood stem cell (PBSC) mobilization failure.Methods: To assess the impact of these regimens on PBSC collection, we performed a retrospective analysis of newly diagnosed MCL patients undergoing induction chemotherapy with R-HyperCVAD versus R-CHOP/R-bendamustine and referred to transfusion medicine for PBSC collection prior to ASCT from 01/2009 to 12/2013. Patients were not allowed any salvage chemotherapy. The primary end point was successful stem cell collection defined as ability to collect ≥2.1 million CD34 cells/Kg. Secondary endpoints were number of days of apheresis, use of pleraxifor as mobilization salvage and total number of CD34+ cells collected.Results: A total of 91 MCL patients were eligible for analysis (Table 1). Patients who received HyperCVAD were younger at the time of collection (median: 56 vs 62 years; p <0.01) and were referred for collection earlier (median time from diagnosis to collection start: 4.5 vs. 6.4 months; p<0.01). There were no other baseline differences between the two groups in terms of gender, bone marrow involvement, stage of disease at presentation and use of plerixafor. While the median number of apheresis days were comparable: 4 (range: 1-9) for the HyperCVAD group and 3 (range: 2-8) for the other group (p=0.21), 18% patients in the Hyper-CVAD group failed to collect adequate numbers of PBSC (defined as < 2.1 ×10 6/Kg) compared to 4% in the other group (p=0.05). Additionally, the median number of CD34+ cells collected was lower in HyperCVAD group (p=0.05). After adjusting for baseline differences in age and timing of collection, for a patient who received HyperCVAD, the odds of failing to collect were 7.28 times higher (95% CI: 1.01, 52.57) than the odds for a patient who received a non-HyperCVAD induction regimen (p=0.05).Ultimately, 81/91 (89%) patients proceeded to high dose chemotherapy and ASCT [82% in HyperCVAD versus 96% in non-HyperCVAD (p=0.06)]. Four of the remaining 10 patients with mobilization failure (all from HyperCVAD arm) proceeded to Allogeneic HCT, the remaining 6 patients did not receive any further treatment.Conclusion: Patients with MCL receiving R-HyperCVAD chemotherapy in the frontline setting have a significantly higher rate of PBSC mobilization failure and collect significantly fewer CD34+ PBSCs when compared to patients treated with comparable regimens. R-HyperCVAD should be used with caution in patients with newly diagnosed MCL who are eligible for ASCT. Some patients failing mobilization may be salvaged with use of plerixafor.Table 1:Patient, Transplant CharacteristicsVariableHyper-CVAD, n=45Median (Range)N (%)Other, n=46Median (Range)N (%)Patient Gender Female Male9 (20) 36 (80)12 (26) 34 (74)Age at Collection Completion (years)56 (40 – 68)62 (36 – 74)Time from Diagnosis to Start of Collection (months)4.5 (2.3 – 65.3)6.4 (3.9 – 69.4)Stage at Diagnosis I II III IV1 (2) 3 (7) 2 (4) 39 (87)2 (4) 1 (2) 6 (13) 37 (81)Bone Marrow Involvement at Diagnosis No Yes Not Done9 (20) 35 (78) 1 (2)13 (28) 32 (70) 1 (2)Treatment after Chemotherapy Auto Transplant Allo Transplant No Transplant37 (82) 4 (9) 4 (9)44 (96) 0 (0) 2 (4)Mozobil Era (08/16/2009) Pre Post8 (18) 37 (82)3 (7) 43 (93)Mozobil Usage No Yes29 (64) 16 (36)30 (65) 16 (35)Number of Collections4 (1 – 9)3 (2 – 8)Total CD344.5 (0.3 – 100.5)5.3 (0.7 – 76.6)Total CD34 (Failure Rate) < 2.1 >/= 2.18 (18) 37 (82)2 (4) 44 (96) DisclosuresChen:Seattle Genetics: Honoraria, Research Funding, Speakers Bureau.

Donor-to-Recipient Weight Ratio Is Independently Associated with CD34+ Yield in Healthy Donors Undergoing Peripheral Blood Stem Cell Collection for Allogeneic Transplantation

Background: Over the past two decades, peripheral blood stem cells (PBSC) have surpassed bone marrow as the preferred graft source for adult allogeneic transplantation due to its more rapid engraftment and potentially better graft-vs-tumor effects, and because PBSC collection is much less invasive for the donor. The optimal CD34+ PBSC dose is ≥ 4.0x106cells/kg, but doses ≥ 8.0x106cells/kg are suggested by some for reduced-intensity conditioning and haploidentical transplants. There is no established minimum CD34+ PBSC dose, but doses below 2.0x106cells/kg have been associated with a higher risk of engraftment delay and failure. There is significant inter-donor variability in the ability to mobilize PBSCs. Several factors have been identified as predictors of PBSC mobilization in healthy donors including: gender, age, weight, body mass index (BMI), and blood counts before and after mobilization. The impact of the donor’s comorbidities on mobilization is currently unknown.Patients/Methods: We performed retrospective chart review of 488 consecutive adult patients who underwent apheresis for allogeneic stem cell donation at Washington University School of Medicine from 2006 through 2013. Patients who received any collection regimen other than 10mcg/kg of G-CSF daily with 20 liters (+/-10%) apheresis on Day 5 were excluded. Patients who had undergone a previous apheresis for stem cell donation were excluded. Univariate analysis was performed to identify predictors of CD34+ PBSC collection in a single apheresis. Variables analyzed were: gender; age; weight; BMI; donor-to-recipient weight ratio; pre and post-mobilization blood counts (white blood count [WBC], hematocrit, platelets, neutrophils, lymphocytes, and monocytes); pre-mobilization glucose and triglyceride levels; post-mobilization peripheral blood (PB) CD34+count; and medical history significant for hypertension, hyperlipidemia, or diabetes mellitus. Subsequently, a linear regression multivariate analysis was performed with all variables found to be significant in the univariate analysis. 2-tailed tests for significance were used throughout the analysis.Results: 304 patients met the eligibility criteria for analysis. The median age was 53 years (range 18-76), 90% were Caucasian, and 50% were male. The median number of CD34+ cells collected was 7.4 x106/kg (range 0.8-27.1). 97% (295) collected ≥ 2.0x106 CD34+cells/kg, 81% (247) collected ≥ 4.0x106 CD34+cells/kg, and 44% (134) collected ≥ 8.0x106 CD34+ cells/kg. Post-mobilization PB CD34+ count (r= 0.841, p <0.001) and donor-to-recipient weight ratio (r= 0.439, p <0.001) were the strongest correlates with CD34+ collection. Weak correlations were seen with post-mobilization neutrophils (r= 0.360, p <0.001), WBC (r= 0.353, p <0.001), and hematocrit (r= 0.207, p <0.001); weight (r=0.280, p <0.001); BMI (r= 0.229, p <0.001); and age (r= -0.207, p <0.001). Male donors collected 9.1x106 CD34+ cells/kg compared to 7.5 x106 CD34+ cells/kg for females, on average (p = 0.003). Hypertension, hyperlipidemia, and diabetes mellitus were not associated with Day 1 CD34+ collection. We performed a multivariate model with the variables: post-mobilization PB CD34+ count; donor-to-recipient weight ratio; gender; post mobilization neutrophil, WBC, and hematocrit; weight; BMI; and age. In this analysis, post-mobilization PB CD34+count, donor-to-recipient weight ratio, and age were all independently significant.Conclusion: After one apheresis, the majority (81%) of donors collected ≥ 4.0x106 CD34+ cells/kg, the optimal number of CD34+ cells for standard allogeneic transplant, but only 44% were able to collect ≥ 8.0x106, the suggested number of CD34+ cells for reduced-intensity or haploidentical transplants. As these reduced-intensity and haploidentical transplants increase in frequency, the need for more accurate predictors of CD34+cell collection will also increase. Donor-to-weight ratio could be a useful tool to stratify potential donors for reduced-intensity and haploidentical transplants. In this study, 63% of donors with a donor-to-recipient weight ratio > 1.0 collected ≥ 8.0x106 CD34+cells/kg, while only 20% of donors with a donor-to-recipient weight ratio ≤ 1.0 did. While gender, weight, and BMI have previously been reported as predictors for CD34+ collection, they potentially were just surrogates for donor-to-recipient weight ratio. DisclosuresNo relevant conflicts of interest to declare.

Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy

Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy

Alemtuzumab/Low Dose Radiation Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with Sickle Cell Disease (SCD)

Allogeneic hematopoietic stem cell transplantation (HSCT) can cure SCD but chemotherapy-based conditioning regimens are associated with substantial morbidity and mortality, particularly in adult patients. A chemotherapy-free, non-myeloablative HSCT with alemtuzumab 1mg/kg divided over 5 days followed by total body irradiation (TBI) 300cGy was recently developed at the National Institute of Health and obtained stable mixed chimerism and clinical cure in 90% of SCD patients receiving an HLA and ABO-matched, related HSCT. The same study was replicated in high risk SCD adult patients at the University of Illinois at Chicago.Thirteen patients aged 17 - 40 years were transplanted between November 2011 and June 2014. Indications included ≥3 vaso-occlusive crises (VOC) per year (n=7), stroke (n=4) and >1 episode of acute chest syndrome (ACS) requiring intensive care (n=2). Unmanipulated, G-CSF mobilized peripheral blood cells were collected from HLA-matched, related donors (MRD) with Hb AS (n=4) or Hb AA (n=9). Four patients had red blood cell (RBC) alloimmunization and 2/13 patients received a graft with major ABO incompatibility. The median number of CD34+ cells infused was 8.1 x 106 cells/kg. Of 13 patients, 10 had severe neutropenia for a median duration of 5 days (range: 1 - 14) and 3 patients had a platelet count < 50 x109/L requiring a platelet transfusion. All patients engrafted and are alive with a median follow-up of 337 days (range: 53 – 986). Cytokine levels involved in T-cell regulation (IL-5, IL-10, and IL-13) increased post-alemtuzumab compared to pre-HSCT levels while no differences were observed in IL-2, IL-4, IL-12 or TNF-α. One secondary graft failure occurred in a patient not compliant with sirolimus and no acute or chronic GVHD has been observed. The median donor chimerism at 1 and 6 months was 96% (range: 63 – 98%) and 84% (range: 41 – 96%), respectively, in blood mononuclear cells; and 48% (range: 20 – 97%) and 25% (range: 20 – 48%), respectively, in CD3+ T cells (Figure 1a). Median hemoglobin concentration increased from 8.4 g/dL (range: 6.6 – 12.4 g/dL) to 12.9 g/dL (range: 11.0 – 16.8 g/dL) and the median reticulocyte percentage decreased from 12.1% (range: 4.8 – 19.6%) to 1.9% (range: 1.3 – 6.2%). Changes in hemoglobin fractionation in HSCT recipients from Hb AA donors are shown in Figure 1b. No episodes of ACS or stroke have been observed following hospital discharge after HSCT. Two patients have been tapered off of sirolimus with stable chimerisms, laboratory values, and no repeat episodes of SCD-related complications.Non-myeloablative HSCT from MRD with alemtuzumab and TBI in SCD adult patients provides a clinical cure in the majority of patients with low toxicity and no transplant-related mortality. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy of Vinorelbine Plus Granulocyte Colony–Stimulation Factor for CD34+ Hematopoietic Progenitor Cell Mobilization in Patients with Multiple Myeloma

We aimed to assess the efficacy of vinorelbine plus granulocyte colony–stimulating factor (G-CSF) for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma and to identify adverse risk factors for successful mobilization. Vinorelbine 35 mg/m2 was administered intravenously on day 1 in an outpatient setting. Filgrastim 5 μg/kg body weight (BW) was given twice daily subcutaneously from day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and be performed for a maximum of 3 consecutive days until at least 4 × 106 CD34+ cells per kg BW were collected. Overall, 223 patients were mobilized and 221 (99%) patients proceeded to leukapheresis. Three (1.5%) patients required an unscheduled hospitalization after chemo-mobilization because of neutropenic fever and renal failure (n = 1), severe bone pain (n = 1), and abdominal pain with constipation (n = 1). In 211 (95%) patients, the leukaphereses were started as planned at day 8, whereas in 8 (3%) patients the procedure was postponed to day 9 and in 2 (1%) patients to day 10. In the great majority of patients (77%), the predefined amount of HPC could be collected with 1 leukapheresis. Forty-four (20%) patients needed a second leukapheresis, whereas only 6 (3%) patients required a third leukapheresis procedure. The median number of CD34+ cells collected was 6.56 × 106 (range, .18 to 25.9 × 106) per kg BW at the first day of leukapheresis and 7.65 × 106 (range, .18 to 25.9 × 106) per kg BW in total. HPC collection was successful in 212 (95%) patients after a maximum of 3 leukaphereses. Patient age (P = .02) and prior exposition to lenalidomide (P < .001) were independent risk factors for a lower HPC amount collected in multiple regression analysis. Vinorelbine plus G-CSF enables a very reliable prediction of the timing of leukapheresis and results in successful HPC collection in 95% of the patients.

HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders

Twenty-three children with nonmalignant disorders received HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) after ex vivo elimination of αβ(+) T cells and CD19(+) B cells. The median number of CD34(+), αβ(+)CD3(+), and B cells infused was 16.8 × 10(6), 40 × 10(3), and 40 × 10(3) cells/kg, respectively. No patient received any posttransplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD). All but 4 patients engrafted, these latter being rescued by a second allograft. Three patients experienced skin-only grade 1 to 2 acute GVHD. No patient developed visceral acute or chronic GVHD. Cumulative incidence of transplantation-related mortality was 9.3%. With a median follow-up of 18 months, 21 of 23 children are alive and disease-free, the 2-year probability of disease-free survival being 91.1%. Recovery of γδ(+) T cells was prompt, but αβ(+) T cells progressively ensued over time. Our data suggest that this novel graft manipulation strategy is safe and effective for haplo-HSCT. This trial was registered at www.clinicaltrials.gov as #NCT01810120.

Autologous peripheral blood stem cell mobilization following high-dose CHOP chemotherapy combined with rituximab in patients with NHL.

e18003 Background: The CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen is an efficient treatment of non-Hodgkin’s lymphoma (NHL). This study was aimed to assess the efficacy and toxicity of high-dose (HD) CHOP ± rituximab on autologous peripheral blood stem cell (APBSC) mobilization for the patients with NHL. In the meantime, factors affecting the collection of CD34+ cells were explored. Methods: 39 patients eligible for autologous stem cell transplantation (ASCT) were included in this retrospective study, 14 patients received HD CHOP combined with rituximab for APBSC mobilization and the others received HD CHOP regimen alone. Results: For all, the median number of CD34+ cell yield was 7.01×106/kg with 37 patients achieving to meet the target CD34+ cell harvest of ≥2.0×106/kg and 27 patients (69.2%) achieved the optimal collection≥5.0×106/kg. 26 of the patients underwent only one apheresis procedure with median CD34+ cell collection of 6.93×106/kg. The mobilization yield of CHO...

Thalidomide, Cyclophosphamide and Dexamethasone Induction Therapy: Feasibility for Myeloma Patients Destined for Autologous Stem Cell Transplantation

This study explored the effect of thalidomide and cyclophosphamide on stem cell collection, in addition to assessing their efficacy as induction therapy for myeloma patients destined for autologous stem cell transplantation (ASCT). We analyzed newly diagnosed myeloma patients who received TCD (thalidomide 100 mg/day for 28 days, oral cyclophosphamide 150 mg/m²/day and dexamethasone 40 mg/day on days 1-4) as induction therapy prior to ASCT. Peripheral stem cells were mobilized with granulocyte colony-stimulating factor and cyclophosphamide. Thirty-six patients (median age 54 years) received TCD chemotherapy (median 4 cycles). The overall response rate to TCD was 77.8% (28/36). The median number of CD34+ cells was 6.5 × 10⁶/kg, and 2 patients failed to achieve the optimal number of CD34+ cells, i.e. 4.0 × 10⁶/kg, although they were able to attain >2.0 × 10⁶/kg. The overall response rate increased up to 94.4% (34/36) after ASCT; this included 9 patients with a stringent complete response without transplantation-related mortality. Four patients died due to disease progression and 17 were found to have progressed after ASCT (the median progression-free survival after ASCT was 19.6 months). TCD chemotherapy can be an effective and feasible induction regimen prior to ASCT for myeloma patients.

Peripheral Blood Stem Cell Mobilization and Engraftment after Autologous Stem Cell Transplantation with Biosimilar rhG-CSF

Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen(®)], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio(®), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 × 5 μg) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU(®), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 × 10(6)/kg (2.22-57.07 × 10(6)/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 × 10(6)/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients. In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.

A Higher Number of CD34+ Cells Collected during Mobilization Is Independently Associated with Successful Engraftment in Autologous Stem Cell Transplant Patients

Introduction Interactions between bone marrow stromal cells and hematopoietic stem cells (HSC) that allow mobilization and subsequent peripheral blood stem cell (PBSC) collection for autologous bone marrow transplantation (ASCT) are similar to interactions that allow successful engraftment after reinfusion. While it has been demonstrated that the cell dose of reinfused CD34+ cells, a surrogate marker for the HSC dose, is an important predictor for engraftment in ASCT, there is little information about the influence of the number of mobilized CD34+ cells on engraftment. We hypothesized that the number of mobilized CD34+ cells can be an indicator for the quality of the surface interactions between HSC and stromal cells and therefore allow prediction of homing potential. We performed a retrospective analysis on patients who underwent PBSC collection and subsequent ASCT at our institution to assess whether efficiency of PBSC mobilization is predictive of engraftment failure. Methods We identified 369 patients who underwent PBSC collection between 01/01/2006-8/31/2012 for a first ASCT at Montefiore Medical Center. We collected data on patient age, sex, use of lenalidomide or thalidomide (“Imid”) prior to mobilization, mobilization regimen (GCSF, GCSF +mozobil, chemo+GCSF, chemo+GCSF+mozobil), number of collections for final cell dose, number of CD34+ cells infused, and the presence of a positive blood culture within 30 days of ASCT. Quintiles were created for the number of CD34+ cells collected. The primary outcome was engraftment failure defined as not achieving an absolute neutrophil count (ANC) >1000/mL or a platelet count >50,000/mL (no platelet transfusion in 500 and a platelet count >20,000/mL without transfusion within </=7 days). We performed a multivariate logistic regression analysis to assess the association of collected CD34+ cells and engraftment failure while adjusting for the other variables. For time to event analyses we used Cox proportional hazard models. Results Median age at ASCT was 58 (range 19-82). 56% of patients were male. Patient-reported race was as follows: Black (38%), White (17%), and “Other” (45%). Indications for ASCT were Multiple Myeloma (45%), Non-Hodgkin Lymphoma (41%), Acute Leukemia (9%), Hodgkin Lymphoma (3%), Amyloidosis (1%), and Germ Cell Tumors (1%). The median number of CD34+ cells collected was 7.7x10 ^6/kg (range 2.26-120 x10 ^6/kg) and median number of CD34+ cells infused was 5.3x10 ^6/kg (2.3-45x10 ^6/kg). Median number of collections for transplant dose was 2 (range 1-8). CD34 cells collected were divided into quintiles (cut points: 6.04, 7.57, 9.86 and 17.7x10 ^6/kg) We found that a higher number of collected CD34+ cells during mobilization was associated with less engraftment failure (p=0.0067): every increase in quintile was associated with a 40% decrease in the risk of engraftment failure (OR 0.60, 95%CI 0.41-0.87). A higher number of collected CD34+ cells was associated with decreased time to platelet engraftment (HR1.15, CI 1.00-1.32, p=0.052), but not with time to ANC engraftment (HR 1.07, p=0.35). Additionally, positive blood cultures within 30 days of ASCT were associated with engraftment failure (p=0.0035), while race, sex, number of collections for the transplanted dose and mobilization regimen did not appear to affect engraftment. Interestingly, we observed that prior Imid use demonstrated a trend toward less engraftment failure (OR 0.41, 95%CI 0.17-1.01; p=0.052). Although a moderate correlation was observed between the variables CD34 cells collected and CD34 cells infused, a sensitivity analysis did not identify a significant difference in model estimations when either variable was omitted. Therefore, it is unlikely that coefficients and variance estimates were affected significantly by the observed collinearity between CD34 cells collected and infused. A larger study is needed to verify these findings, as the impact of collinearity often diminishes with sample size. Conclusion The number of CD34+ cells collected independently predicts successful engraftment and Imid use prior to mobilization may protect against engraftment failure. A possible explanation for these findings is that alterations in the bone marrow environment influence mobilization and later engraftment of HSC. Disclosures: Barta: Onyx: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen Pharmaceuticals: Speakers Bureau; Seattle Genetics: Membership on an entity’s Board of Directors or advisory committees; Otsuka: Research Funding.

CD4+T-cell recovery after initiation of antiretroviral therapy in a resource-limited setting: A prospective cohort analysis

CD4(+) T-cell count recovery after antiretroviral therapy (ART) initiation is associated with improved health outcomes. It is unknown how the CD4(+) T-cell counts of African HIV patients recover following ART initiation. We examined CD4(+) T-cell count recovery in a large cohort of HIV-positive patients initiating ART in Uganda between 2004 and 2011. We categorized patients according to their CD4(+) T-cell count at ART initiation. All patients received CD4(+) T-cell count evaluations on a biannual basis. We used quantile regression to model the recovery of CD4(+) T-cells during ART. A total of 5,271 patients aged ≥14 years at baseline were included. The median number of CD4(+) T-cell count measurements was 6 (IQR 4-8), and vital status at censoring was known in 97.2% of individuals. Most CD4(+) T-cell count recovery occurred within the first 12 months, with marginal increases beyond 18 months and stabilization after 5 years. The strongest predictor of CD4(+) T-cell count recovery was baseline CD4(+) T-cell count. After 5 years on treatment, the median CD4(+) T-cell count was 334 cells/mm(3) for patients initiating ART with <100 cells/mm(3). Only those initiating ART with >200 cells/mm(3) reached a 5-year median >500 cells/mm(3). Adolescents had the most robust CD4(+) T-cell count recovery with a median increase after 12 months that was 109 cells/mm(3) greater than those initiating ART at age ≥50 years. In individuals from a resource-limited setting, baseline CD4(+) T-cell count was highly predictive of the maximum CD4(+) T-cell count level achieved while on ART.

High‐dose methotrexate in the mobilization of hematopoietic stem cells for patients with non‐Hodgkin's lymphoma: a twelve‐year study in a single center

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) is a promising approach for non-Hodgkin's lymphoma (NHL). Higher cell doses have been associated with a faster blood count recovery and a reduction in transfusion requirements, infection rates, and hospitalization times. Mobilization failure constitutes one of the main reasons for avoiding auto-HSCT. The role of high-dose methotrexate (MTX) as mobilization regimen is still unclear. The effect of high-dose MTX as a mobilization regimen for 67 adult patients with NHL who received auto-HSCT was studied between January 2001 and October 2012. The stem cells were mobilized using combination chemotherapy including MTX plus granulocyte-colony-stimulating factor (G-CSF) in 33 patients (Group A), and the stem cells of the other 34 patients were mobilized using the same combination chemotherapy plus G-CSF without MTX (Group B). All of the patients were successfully mobilized in Group A; however, two patients failed in Group B. The median numbers of CD34+ cells collected were 14.36 × 10(6) and 5.3 × 10(6) cells/kg for Groups A and B, respectively (p < 0.05). All of the patients experienced a stable neutrophil and platelet (PLT) engraftment. The times to white blood cell engraftment were 8.0 days in Group A and 11.0 days in Group B, and the times to PLT engraftment were 12.0 days in Group A and 13.0 days in Group B (p < 0.05 for both variables). High-dose MTX is a powerful regimen component for stem cell mobilization in adult patients with NHL.