Higher Median CD34 Research Articles

Evomela® Significantly Increases the Risk of Engraftment Syndrome in Patients with Multiple Myeloma Treated with Autologous Stem Cell Transplantation

Evomela® Significantly Increases the Risk of Engraftment Syndrome in Patients with Multiple Myeloma Treated with Autologous Stem Cell Transplantation

Clinical and cost outcomes of pre-emptive plerixafor administration in patients with multiple myeloma undergoing stem cell mobilization

PurposeThe stem cell mobilization agent plerixafor significantly improves CD34+ stem cell procurement in patients with multiple myeloma undergoing autologous stem cell transplant. We compared mobilization success rates and costs of two regimens of plerixafor administration: pre-emptive (P-PL, initiated the evening prior to the first day of stem cell collection) and standard (S-PL, initiated the evening prior to the second day of stem cell collection in the event of inadequate collection on the first day). MethodsPatients with multiple myeloma undergoing mobilization were categorized as either P-PL or S-PL. Stem cell collection success was evaluated using logistic regression models. Associated costs were aggregated in terms of average collections per patient in each mobilization option (patient level), and escalated to a panel of 5000 patients (population level). Results299 patients were evaluable; 241 received P-PL and 58 received S-PL. Patients receiving P-PL had higher median CD34+ count pre-collection and higher median total CD34+ cell harvest on the first collection (6.75 × 106/kg for P-PL, 1.96 × 106/kg for S-PL; P<0.01). In multivariable analyses, P-PL remained significantly associated with the ability to collect ≥2 × 106/kg CD34+ on the first day (OR = 4.05, 95% CI, 1.19–13.83, P = 0.03) and ≥5 × 106/kg CD34+ in total (OR = 3.09, 95% CI, 1.04–9.23, P = 0.04). P-PL saved $11,248 (46%) per patient compared with S-PL. ConclusionP-PL significantly enhanced collection efficiency, with most patients completing collection in 1 day, resulting in substantial cost savings.

Evaluation of Cord Blood (CB) TNC & CD34+ Cell Content, Cell Dose & Donor-Recipient 8-Allele HLA-Match By Patient Ancestry: An Analysis of 544 Units in a Racially & Ethnically Diverse Patient Population

Introduction Optimal CB unit selection incorporates TNC & CD34+ cell dose & 8-allele donor-recipient HLA-match. How graft characteristics for these parameters vary by patient (pt) race/ ethnicity, however, is unknown. Methods We analyzed cryopreserved TNC & CD34+ cell content, the cell dose incorporating pt weight, & HLA-match of infused & backup (reserved but not shipped) units by pt ancestry in CB transplant (CBT) recipients transplanted 7/2013-6/2018. Units were chosen based on banking practices, TNC & CD34+ dose & 4-6/6 & 8-allele HLA-match. Patient (pt) racial/ ethnic origins were prospectively obtained & grouped per Barker J. et al, BBMT 2010. Results The characteristics of 544 units chosen for 144 diverse CBT recipients by pt ancestry are shown (Table 1). 286 units were infused (142 doubles, 2 singles) & pts had a total of 258 backup units (0-2/pt). The median TNC content of units for Europeans was higher than for Non-Europeans (216 vs 197, p = 0.002). Units for NW Europeans had the highest median TNC content with lowest in units for Africans & White Hispanics. Units chosen for Europeans also had a higher median CD34+ cell content than Non-Europeans (160 vs 132, p = 0.007). Units for NW Europeans had the highest & units for Africans the lowest median CD34+ content. Median TNC/kg was similar in units for European & Non-European pts (2.7 vs 2.5, p = 0.11) & differences between groups were not marked. However, there was a trend for units for Europeans having a higher median CD34+ dose than units for Non-Europeans (1.9 vs 1.7, p = 0.057) with disparity between groups. Although the median 8 allele HLA-match was 5/8 for units chosen for both European & Non-European pts, units identified for non-Europeans were more mismatched (p = 0.017). When the 286 transplanted units (considered the best) were analyzed, the median TNC & CD34+ contents of units were higher for Europeans than non-Europeans (232 vs 216, p = 0.022, & 181 vs 152, p = 0.009). As shown in Table 2, while there were no overall differences in the median TNC & CD34+ doses of units for Europeans & non-Europeans, differences in cell content combined with differences in weights resulted in TNC & CD34+ dose disparities within ancestry groups. For example, NW Europeans (high weight, high CD34+ content) had the highest CD34+ doses; lower content in Asian pts was partially compensated for by low weight; African pts (high weight, low content) had the lowest doses. Finally, there was marked differences in HLA-match distribution by ancestry group: eg only 23% of units for NW Europeans were 3-4/8 vs 40% for S. Europeans, 46% for white Hispanics & 51% for Africans. Conclusions CB extends transplant access to minorities but differences in cellular content translates to many ancestry groups pts having access to only lower dosed units. There are also marked racial/ ethnic disparities in HLA-match. This data supports continued funding of banks to further increase the CB inventory.

Evaluation of Cord Blood (CB) Unit TNC & CD34+ Cell Content & Donor-Recipient High-Resolution 8 HLA-Allele Match By Patient Ancestry: An Evaluation of 513 CB Units in a Racially & Ethnically Diverse Population of Adults with Hematologic Malignancies

Introduction: Optimal CB unit selection guidelines recommend consideration of CD34+ cell dose & 8-allele donor-recipient HLA-match. How graft characteristics for these parameters vary by patient (pt) race/ ethnicity, however, is not known.Methods: We analyzed the infused graft & back-up unit cryopreserved total nucleated cell (TNC) x 107 & CD34+ x 105 cell content, the cell dose (incorporating pt weight), & 4-6/6 & 8-allele HLA-match by pt ancestry in CB transplant (CBT) recipients transplanted 1/2014-6/2018. Units were chosen based on banking practices (e.g. RBC depleted, standard cryo volumes), TNC & CD34+ dose & 4-6/6 & 8-allele HLA-match with dose usually taking priority over match given pt size at our center. The analysis included transplanted units (considered the best choice) & the next best high resolution typed back-up units (reserved but not shipped). Pt racial/ ethnic origins were prospectively obtained by detailed family history & grouped as previously described (Barker J. et al. BBMT 2010).Results: The characteristics of 513 units chosen for 136 CBT recipients by pt ancestry are shown (Table 1). Pts had highly diverse origins including 70 (51%) non-Europeans. The 513 units included 270 units infused as the graft (134 doubles & 2 singles) & 243 back-up units (109 pts had 2 back-ups, 25 pts had one & 2 had none). Thus, 4 best units were analyzed in 109 pts (all double unit recipients), 3 best in 25 pts (all doubles), & 1 unit in 2 pts (both singles). The median weight of the 136 pts was 81 kg. Asian pts (median 68 kg) had a lower weight than other groups. The median TNC content of units for the 66 European pts was higher than that for the 70 Non-Europeans (218 vs 196, p = 0.004). Units chosen for Northwestern (NW) Europeans had the highest median TNC content (235) with lower TNC content in units for Southern Europeans (202), Asian (193), African (191) & White Hispanic (189) pts. Units chosen for European pts also had a higher median CD34+ cell content (162) than Non-Europeans (138), p = 0.004. NW Europeans had units with a higher median CD34+ content (198) & the lowest CD34+ content were those for African (124) & Middle Eastern pts (124). When patient weight was considered, median TNC/kg dose per unit was similar in European and Non-European pts (2.7 vs 2.6, p = NS). Units for NW Europeans had the highest median TNC dose (3.0) whereas those for African pts had the lowest TNC dose (2.4). Units for Europeans had a higher median CD34+ dose (2.0) than Non-Europeans (1.7) although this difference was not significant (p = 0.15). Additionally, similar to TNC dose, median CD34+ dose was highest in units for NW European pts (2.2) & lowest in units chosen for African pts (1.5). 89% of chosen units were 4/6 HLA-matched with no differences between Europeans & non-Europeans. Furthermore, the median 8 allele HLA-match was 5/8 (range 2-8/8) with no overall differences between units for Europeans and Non-Europeans (p = NS).When only transplanted units were analyzed (Table 2), the median TNC & CD34+ contents were significantly lower in non-Europeans than Europeans (238 vs 216, p = 0.01 & 184 vs 160, p = 0.016). Overall, however, units received by Europeans vs non-European pts had similar TNC & CD34+ doses (p = NS). However, differences in the CD34+ content combined with differences in pt weights resulted in disparities in CD34+ doses by ancestry sub-group. NW Europeans (high weight, high CD34+ content) received the best CD34+ doses; lower CD34+ content in Asian pts was compensated for by their lower weight. African pts (high weight, low CD34+ content) received the lowest CD34+ doses. The median 8 allele HLA-match for all was 5/8 (range 3-8/8) with the exception of African pts [median 4/8 (range 3-7/8)]. Moreover, while 108 (40%) of transplanted units were 3-4/8 HLA-matched overall, there were marked differences between pt sub-groups with only 23% of units for NW Europeans being 3-4/8 vs 42% for southern Europeans, 46% for white Hispanics & 53% for Africans.Conclusions: While CB significantly extends transplant access to racial & ethnic minorities, differences in cellular content translates to many minority pts receiving lower dosed units. There are also marked racial/ ethnic differences in HLA-match grade with African pts the most likely to receive highly mismatched units. This data supports ongoing funding of public CB banks to further increase the inventory of high dosed & better matched units for all but especially racial & ethnic minority pts. [Display omitted] DisclosuresShah:Janssen: Research Funding; Amgen: Research Funding. Kernan:National Cancer Institute: Research Funding.

Low-Dose Antithymocyte Globulin for Graft-versus-Host-Disease Prophylaxis in Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation

Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in vivo T cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates in many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Understanding that higher rates of GVHD are observed with matched unrelated donor (MUD) versus matched related donor (MRD) alloHCT, at our institution MUD alloHCT recipients have historically had low-dose Thymoglobulin (total dose, 2.5 mg/kg; Genzyme-Sanofi, Cambridge, MA) added to our standard MRD GVHD prophylaxis regimen. In this retrospective cohort study we assessed post-HCT the effectiveness of our uniquely low-dose ATG strategy by comparing ATG exposed (MUD) and unexposed (MRD) alloHCT recipients for GVHD and other clinical HCT outcomes. This retrospective single-center study included all HCT patients transplanted for any malignant indication at The Ottawa Hospital from 2009 to 2014. MUD patients received rabbit ATG (Thymoglobulin) at a total dose of 2.5 mg/kg given over 2 days (.5 mg/kg on day –2; 2.0 mg/kg on day –1 before stem cell infusion) in addition to standard GVHD prophylaxis. Primary outcomes assessed were incidence of acute and chronic GVHD, defined as new-onset GVHD requiring systemic immunosuppressive therapy at less or more than 100 days, respectively. Secondary outcomes included disease relapse and survival. There were 110 and 77 patients in the ATG exposed (MUD) and unexposed (MRD) cohorts, respectively. At baseline there were no significant differences in median age at transplant, sex, disease indication or risk index, graft source, conditioning regimen, or intensity between cohorts. A higher proportion of 7/8 mismatched donor transplants (13% versus 3%, P = .02) and a higher median CD34+ dose (7.9 versus 4.9 × 108 cells; P < .01) was observed in the ATG exposed cohort. No differences were noted in platelet engraftment. ATG exposed patients had significantly shorter time to neutrophil engraftment than the unexposed cohort (16 versus 19 days, respectively; P < .01). ATG exposed patients had significantly lower rates of GVHD than ATG unexposed patients (57% versus 79%; P = .01), with differences predominantly in rates of chronic GVHD (18% versus 44%, P < .01). At median follow-up of 28 (range, 3 to 69) and 25 (range, 2 to 73) months for survivors in ATG exposed and unexposed cohorts, respectively, no significant differences in overall survival (median overall survival not met for either cohort), relapse incidence (26% versus 29%, P = .73), or relapse-free survival (RFS) (not met in ATG exposed and 26 months in ATG unexposed, P = .22) were observed between groups. The ATG exposed cohort had significantly higher GVHD-free RFS (GRFS) with a 2-year GRFS of 23% versus 3% (P = .003). There were no significant differences between cohorts in proportion of patientswith post-HCT infectious episodes or intensive care unit admissions. Here we report significantly lower rates of chronic GVHD and significant improvement in GRFS in an ATG exposed MUD alloHCT cohort compared with an ATG unexposed MRD cohort. These findings were observed without differences in relapse, survival, infectious complications, or intensive care unit admissions. Our findings highlight the association of unconventionally low-dose ATG with improved GVHD outcomes and suggest a need for prospective study of ATG use in lower doses.

Superior Quality of Life Scores in Patients Over 60 Years of Age in Allogeneic Hematopoietic Cell Transplant.

AbstractAbstract 3068Advanced age is becoming less of a barrier to allogeneic hematopoietic cell transplantation (HCT) and transplantation has become an established standard of care for many older patients (pts) with hematologic malignancies. We previously reported superior quality of life (QOL) scores in pts age 60 and over undergoing high dose chemotherapy and autologous stem cell transplant compared with pts less than 60 (Dabney J et al, Blood 2008 112: Abstract 2381). These data prompted us to evaluate QOL assessments in pts≥60 undergoing allogeneic HCT compared to pts<60 years.435 adult pts underwent allogeneic HCT from June 2003 to December 2010. Prospective psychometric instruments were administered to 304 pts <60 years of age (median 47, range 18–59) and 47 pts≥60 years of age (median 62, range 60–70) with acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, non-Hodgkins lymphoma, Hodgkins disease, myeloproliferative neoplasms, aplastic anemia, and plasma cell neoplasms. Psychometric data was assessed longitudinally (at baseline, first post-discharge visit, day 100, 180, and 365) by validated questionnaires: Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), coping inventory (Brief COPE), and the Profile of Mood State- Short Form (POMS). The FACT-BMT measures five components of QOL: physical well being (PWB), social well being (SWB), emotional well being (EWB), functional well being (FWB), and additional concerns (AC). The POMS measures depression, vigor, anger, tension, confusion and fatigue. Brief COPE has 14 coping skills, such as use of emotional and instrumental support, venting, and positive reframing. Secondary endpoints included overall survival (OS), relapse-free survival (RFS), incidence of acute and chronic graft versus host disease (GVHD), and relapse. Imbalances between the two groups (p<0.01 for all) included comorbidity index (HCT-CI), (62% of pts<60 with a comorbid score of >1 compared to 74% in pts≥60), preparative regimen, (84% myeloablative in pts <60, 21% in pts ≥60%), and source of hematopoietic cells, (29% peripheral stem cells in pts<60 versus 72% in pts≥60), with a higher median CD34+ cell dose (4.51×106/kg in pts≥60) compared with pts<60 (2.51×106/kg).Psychosocial functioning and QOL differences were compared between age groups over time by repeated measures analysis of variance, using intensity of transplant as a variable given the imbalance. On FACT, pts≥60 reported better social (p=0.006) and functional well being (p=0.05), and had better total FACT scores, (p=0.043) across all time points. On POMS, pts≥60 reported less fatigue than patients<60 (p=0.01), while COPE assessment indicated that older pts reported worse use of planning (p=0.012) and humor (p=0.041) compared with younger pts. Pts≥60 years also reported worse scores for active coping, but only at day 365 (p=0.019), and scored worse on behavioral disengagement at the first post-transplant time point (p=0.016), but this difference became non-significant by day 100 (p=0.81). With a median follow up of 49 months, there were no significant differences in OS, RFS, relapse, or chronic GVHD. There was a lower incidence of grade 3–4 acute GVHD in pts≥60 compared to pts<60, (6.4% versus 15.8% at 6 months, p=0.016).This study provides further evidence that advanced age should not be a barrier in the decision to pursue allogeneic HCT. Older pts achieved better total scores in QOL assessments when compared to younger pts. One can hypothesize that older pts are more likely to have experienced adversity or family and personal health related problems, making them better able to endure symptoms than younger pts. In addition, younger pts may be more affected due to non-health related concerns including the adverse effect of transplantation on their careers, family, and finances. While our older population has proven to have similar medical outcomes and improved QOL, younger pts may benefit from social work interventions that focus on adapting to changes in functioning and social well-being. [Display omitted] [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Intravenous Compared to Oral Busulfan with Cyclophophamide for Allogeneic Hematopoietic Progenitor Cell Transplant Conditioning for AML and MDS.

AbstractAbstract 3475Busulfan (Bu) is commonly used with cyclophosphamide (Cy) as a conditioning regimen for allogeneic hematopoietic progenitor cell transplantation (HPCT). Recently, intravenous (IV) Bu has often replaced oral Bu for conditioning. We have previously reported that substituting IV for oral Bu was associated with a lower rate of relapse, and superior relapse-free and overall survivals for relapsed or refractory non-Hodgkin lymphoma patients undergoing autologous HPCT (Dean et al. Br J Haematol 2010 Jan;148(2):226-34). We retrospectively compared the outcomes of 135 consecutively treated AML and MDS patients who underwent allogeneic HPCT at our institution from 5/2001 through 10/2009 with BuCy using oral (n = 93) or IV (n = 42) Bu, without dose adjustment. The analysis included matched related (n=97) and 8/8 HLA matched unrelated donors (n=38). Oral Bu was administered as 1 mg/kg every 6 hours for 16 doses while IV Bu was administered as 0.8 mg/kg every 6 hours for 16 doses (days –8 through -4) followed by Cy 60 mg/kg/day × 2 (days –3 and –2). The IV Bu patients were older (median age 49 vs. 47 yrs, respectively, p=0.037), more commonly had unrelated donors and peripheral blood stem cells for their HPCT cell source than those treated with oral Bu. There were no significant differences between the groups with regards to patient gender, race, CIBMTR comorbidity index score, number of prior chemotherapy regimens, pre-transplant disease status (each group had 45% of patients in CR1 or CR2), donor-recipient gender relationships or nucleated cell dose infused. The IV Bu group had a higher median CD34+ cell dose infused than those who received oral Bu (3.34 vs. 2.19 ×106/kg, respectively, p=0.028). The IV Bu patients experienced a significantly lower incidence of mucositis (3% vs. 55%, p<0.001) and less severe mucositis (median OMAS scores 0 vs.0.08, respectively, p<0.001). However, there were no significant differences between the IV and oral Bu groups in days until neutrophil and platelet count engraftment, length of transplant hospitalization, incidence of acute or chronic GVHD, sinusoidal obstruction syndrome, and 100 day mortality. At this time 26 (62%) of the IV Bu patients and 33 (36%) of the oral Bu patients are alive, however, the median follow-up was substantially longer for the oral Bu group (50 vs. 13 months, p<0.001). Disease relapse was the most common cause of death for both the IV and oral Bu patients accounting for approximately 50% of deaths in each group. The 1 and 2 year transplant-related mortality for the IV Bu patients was 21% for both, while that for the oral Bu group was 23% and 29%, respectively. The 1 and 2 year relapse mortality for the IV Bu patients was 21% for both, while that for the oral Bu group was 24% and 29%, respectively. Substituting IV for oral Bu reduces variability in drug exposure and potentially improves safety as suggested from our finding of significantly less severe oral mucositis in the IV Bu group. Further follow-up of the IV Bu group is required to adequately assess for a survival benefit. Whether pharmacokinetic-based Bu dosing can improve outcomes after allogeneic HPCT in this setting is worthy of further study. Disclosures:Sobecks:Otsuka Pharm.: Research Funding.

Effective Primary Mobilization of Autologous Peripheral Blood Stem Cells with Granulocyte Colony-Stimulating Factor and Plerixafor in Lenalidomide-Treated Patients with Multiple Myeloma

AbstractAbstract 2254 Background:Lenalidomide (LEN) is extensively used in combination with dexamethasone (DEX), with or without bortezomib (BOR), for initial treatment of multiple myeloma (MM). However, several studies have shown that previous exposure to LEN is associated with impaired collection of autologous peripheral blood stem cells (PBSCs) after mobilization with either granulocyte-colony stimulating factor (G-CSF) or chemotherapy plus G-CSF. The effects of previous exposure to LEN on the collection of autologous PBSCs after mobilization with G-CSF plus plerixafor (PLX; Mozobil®) are not well described. Methods:We evaluated the outcomes of autologous PBSC mobilization and collection in 15 consecutive patients (pts) with MM who received previous treatment with at least 2 21-day cycles of LEN in combination with either DEX (10 pts) or DEX and BOR (5 pts) and who underwent initial autologous PBSC mobilization with G-CSF (10 micrograms/kg/dose subcutaneously daily × 4 days) and PLX (0.24 mg/kg/dose subcutaneously, after fourth dose of G-CSF), with additional doses of G-CSF and PLX for subsequent apheresis sessions. Results:Median age of pts was 58 yr (range, 35–67). Patients received a median of 5 cycles (range, 2–12) of LEN. The median number of apheresis sessions was 1 (range, 1–2). The median level of CD34+ cells in the peripheral blood at day 1 of apheresis was 84.36 per microliter (range, 12.46–167.37), and the median yield of CD34+ cells was 6.52 × 106/kg (range, 1.43–17.11) after day 1 of apheresis and 7.46 × 106/kg (range, 2.32–17.11) after day 2 of apheresis. No LEN-treated pts failed mobilization (defined as collection of less than 2 × 106 CD34+ cells/kg). Eleven pts (73.3%) collected at least 6 × 106/kg CD34+ cells (i.e., sufficient for 2 transplants) after 1 or 2 aphereses, with 8 pts (53.3%) reaching that target after 1 apheresis. Of the 4 pts (26.7%) in whom fewer than 6 × 106/kg CD34+ cells were collected after 2 aphereses, 3 pts collected at least 4 × 106 CD34+ cells/kg, and only 1 pt (who received only 2 cycles of LEN) collected 2.32 × 106/kg CD34+ cells. The number of cycles of LEN did not correlate with concentration of CD34+ cells in peripheral blood on day 1 of apheresis (r2=0.099), yield of CD34+ cells on day 1 of apheresis (r2=0.108), or total yield of CD34+ cells after 2 days of apheresis (r2=0.067). Pts who received 4 or fewer cycles of LEN had higher median circulating CD34+ cells on apheresis day 1, higher median CD34+ cell yield with day 1 apheresis and higher total CD34+ cell yield after 2 aphereses than pts who received more than 4 cycles of LEN (Table). Five of 6 pts who received 4 or fewer cycles of LEN collected at least 6 × 106 CD34+ cells/kg after 1 apheresis, compared with 3 of 9 pts who received more than 4 cycles. However, none of these differences were statistically significant (Table). Conclusions:Previous treatment with LEN does not impair collection of autologous PBSCs after initial mobilization with G-CSF and PLX. However, there was a trend to more robust autologous PBSC collections and decreased need for second aphereses in pts who received fewer cycles of LEN. These findings are consistent with the recommendation of the International Myeloma Working Group to collect autologous PBSCs from MM pts after 4 or fewer cycles of LEN-containing regimens. As mobilization with G-CSF with or without chemotherapy leads to inconsistent autologous PBSC collection in LEN-treated MM pts, our experience supports the use of G-CSF plus PLX as an upfront mobilization strategy for these pts. Disclosures:No relevant conflicts of interest to declare.

Relationship of Harvest CD34+ and CD3+ Counts To Chronic Graft-Versus-Host Disease (cGVHD), Relapse and Survival Following Sibling Allogeneic Stem Cell Transplant.

G-CSF mobilized peripheral blood stem cells are increasingly used as a source of cells for sibling allogeneic transplantation. In comparison with bone marrow transplants (BMT), peripheral blood stem cell transplants (PBSCT) have been associated with increased chronic graft-versus-host disease (cGVHD). In order to examine the relationship between CD34+ and CD3+ counts and the development of cGVHD, we analyzed the outcome of patients from an international database of nine randomized trials comparing PBSCT and BMT. There were a total of 1111 patients: 305 patients developed extensive cGVHD, 261 limited cGVHD, 368 had no cGVHD and 177 did not have adequate information concerning cGVHD for analysis. We excluded patients with limited cGVHD because this can be a difficult diagnosis to make with certainty. We also excluded those without adequate data and thus the analysis is based on 673 patients (305 with extensive cGVHD and 368 with no cGVHD). There was no common baseline hazard for the development of extensive cGVHD among studies and thus the analysis was stratified by study. The primary outcomes were time to development of extensive cGVHD and time to the composite endpoint of death or relapse. Harvest CD34+ and CD3+ counts were analyzed as dichotomous variables based on the median cell counts. In the PBSCT group, the median CD34+ and CD3+ counts were 6.05 and 288.01×106/kg and in the BMT group, the median CD34+ and CD3+ counts were 2.89 and 32.79×106/kg respectively. As previously reported, there was an increased risk of developing extensive cGVHD with PBSCT compared to BMT (hazard ratio 1.77, 95% CI 1.39–2.23). The time to develop extensive cGVHD was not affected by the CD34+ or CD3+ count within either the PBSCT or BMT group. In addition, the composite endpoint of death or relapse was also not affected by either the CD34+ or CD3+ count in the PBSCT group. However, in the BMT group, a higher median CD3+ count was associated with an increased risk of death or relapse (p=0.04). Furthermore, a higher median CD34+ count was associated with a trend to a decreased risk of death or relapse (p=0.09). In summary, we confirm the higher risk of developing extensive cGVHD with PBSCT compared to BMT. In this analysis, we did not find a relationship between CD34+ and CD3+ counts and the risk of extensive cGVHD within either the PBSCT or BMT groups. However, our analysis suggests an association between higher median CD3+ counts and an increased risk of death or relapse in the BMT group. If this observation is confirmed, further studies are required to determine whether the higher CD3+ cell content of the marrow graft exerts a direct effect on the risk of relapse or death, or whether it is a surrogate for a less effective marrow harvest.

Birthweight of full-term infants is associated with cord blood CD34+ cell concentration

CD34+ cell counts are used to define the haematopoietic stem cell potential of a given cord blood transplant. The aim was to test the hypothesis that high concentration of cord blood haematopoietic progenitor and stem cells could be a reflection of intrauterine growth, of which birthweight is an indicator. Simple and multiple regression analyses were applied to test cord blood bank data on 1368 infants for associations of selected obstetric factors and cellular contents of cord blood. When groups were formed based on the extreme values (5th versus 95th percentiles) of a given variable, e.g. birthweight, the term infants having the highest birthweights were found to have statistically significantly higher median cord blood CD34+ cell concentrations. Also, infants in the top 50th percentile of relative birthweight had higher median CD34+ cell concentration than infants in the low 50th percentile. In multiple regression analysis, the correlation between birthweight and CD34+ cell concentration was statistically clearly significant. Notably, while an expected correlation between gestational age and nucleated cell concentration was found, there was no association between infant gestational age and CD34+ cell concentration. Haematopoietic progenitor and stem cells may reflect intrauterine growth and have a more central role in foetal development than has been reported earlier.

Birthweight of full‐term infants is associated with cord blood CD34+ cell concentration

Aim: CD34+ cell counts are used to define the haematopoietic stem cell potential of a given cord blood transplant. The aim was to test the hypothesis that high concentration of cord blood haematopoietic progenitor and stem cells could be a reflection of intrauterine growth, of which birthweight is an indicator. Methods: Simple and multiple regression analyses were applied to test cord blood bank data on 1368 infants for associations of selected obstetric factors and cellular contents of cord blood. Results: When groups were formed based on the extreme values (5th versus 95th percentiles) of a given variable, e.g. birthweight, the term infants having the highest birthweights were found to have statistically significantly higher median cord blood CD34+ cell concentrations. Also, infants in the top 50th percentile of relative birthweight had higher median CD34+ cell concentration than infants in the low 50th percentile. In multiple regression analysis, the correlation between birthweight and CD34+ cell concentration was statistically clearly significant. Notably, while an expected correlation between gestational age and nucleated cell concentration was found, there was no association between infant gestational age and CD34+ cell concentration. Conclusion: Haematopoietic progenitor and stem cells may reflect intrauterine growth and have a more central role in foetal development than has been reported earlier.