Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies

Unrelated cord blood transplantation (CBT) has now become more common, but as yet there have been only a few reports on its outcome compared with bone marrow transplantation (BMT), especially for adults. We studied the clinical outcomes of 113 adult patients with hematologic malignancies who received unrelated BM transplants (n = 45) or unrelated CB transplants (n = 68). We analyzed the hematopoietic recovery, rates of graft-versus-host disease (GVHD), risks of transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. The time from donor search to transplantation was significantly shorter among CB transplant recipients (median, 2 months) than BM transplant recipients (median, 11 months; P < .01). Multivariate analysis demonstrated slow neutrophil (P < .01) and platelet (P < .01) recoveries in CBT patients compared with BMT patients. Despite rapid tapering of immunosuppressants after transplantation and infrequent use of steroids to treat severe acute GVHD, there were no GVHD-related deaths among CB transplant recipients compared with 10 deaths of 24 among BM transplant recipients. Unrelated CBT showed better TRM and DFS results compared with BMT (P = .02 and P < .01, respectively), despite the higher human leukocyte antigen mismatching rate and lower number of infused cells. These data strongly suggest that CBT could be safely and effectively used for adult patients with hematologic malignancies.     

Improved disease-free-survival after transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical unrelated donors in patients with first chronic phase chronic myeloid leukemia

Outcomes after peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (n = 37) were compared with outcomes after bone marrow transplantation (BMT) (n = 54) in the HLA-compatible unrelated donor setting. Median follow-up was 17 months after PBSCT and 29 months after BMT. Both neutrophil and platelet recovery were faster after PBSCT (P <.05). PBSCT was associated with improved immune reconstitution, with higher peripheral blood naive (CD4(+)CD45RA(+)) and memory (CD4(+) CD45RO(+)) helper T cells at 3 months and 12 months after transplantation (P <.03). The cumulative incidence of acute (grades II-IV) and chronic graft-versus-host disease (GVHD) were similar, but BMT was associated with a higher cumulative incidence of severe, acute (grade III-IV) GVHD at 24% as compared with 8% with PBSCT (P <.05). Molecular relapse, defined by 2 consecutive positive polymerase chain reaction assays for bcr-abl within a 4-week interval, occurred in 12 of 45 evaluable patients (27%) after BMT and in 4 of 37 (11%) after PBSCT (not significant). Cytogenetic relapse occurred in 5 of 54 patients after BMT (9%) and in 1 of the 37 (3%) patients after PBSCT (not significant). Seventeen of the 54 patients died after BMT (31%), as compared with 2 of 37 patients after PBSCT (5%). Deaths in the BMT group were associated mainly with infections and severe, acute GVHD. The estimated probability of transplant-related mortality (TRM) and disease-free survival at 1000 days after receiving the transplant were 30% and 64% in the BMT group and 5% and 91% in the PBSCT group (P <.03). Overall survival 1000 days after receiving the transplant was 66% after BMT and 94% after PBSCT (P <.02). In the multivariate analysis, only acute GVHD significantly influenced TRM (P <.01).     

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

Older recipient and donor age were associated with higher incidences of severe graft‐versus‐host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38–74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant‐related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD‐free, relapse‐free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT. Am. J. Hematol. 91:E284–E292, 2016. © 2016 Wiley Periodicals, Inc.     

Comparison of allogeneic T cell-depleted peripheral blood stem cell and bone marrow transplantation: effect of stem cell source on short- and long-term outcome.

We report the results of a retrospective single-center study comparing engraftment, acute and chronic GVHD, relapse and survival in patients with malignant hematological disorders transplanted with allogeneic peripheral blood stem cells (alloPBSCT, n = 40) or bone marrow cells (alloBMT, n = 42). All transplants were T cell depleted by in vitro incubation with the Campath-1 monoclonal antibody. Primary graft failure occurred in none of the patients receiving an alloPBSCT compared with 3/42 of the recipients of an alloBMT. In addition, two patients in the alloBMT group showed no platelet engraftment. Recipients of PBSC had a more rapid recovery of neutrophils (median 14 days) compared to BM transplant recipients (median 32 days). Platelet recovery was also accelerated in PBSC recipients compared to BM recipients (11 vs 38 days). There was an increase in the incidence of grade II acute GVHD and chronic GVHD in patients after alloPBSCT (18% and 23%, respectively) compared to patients receiving alloBMT (5% and 8%, respectively). The 2-year cumulative incidence of relapse was similar in both groups (47%). At 6 months after transplantation, transplant-related mortality (TRM) was lower in PBSCT recipients than in BMT recipients. However, at a follow-up of 3 years TRM was similar in both groups. The disease-free survival rate at 3 years after transplantation did not differ between the groups (42% for PBSCT and 41% for BMT recipients). Our results indicate that T cell-depleted alloPBSCT compared to alloBMT is associated with a more rapid hematopoietic reconstitution and a decreased TRM at 6 months follow-up after transplantation. However, at a follow-up of 3 years, no sustained survival benefits were observed.     

前列腺素E脂质微球联合小剂量肝素及丹参预防60例异基因造血干细胞移植后肝静脉闭塞病

目的:探讨前列腺素E脂质微球联合小剂量肝素及复方丹参预防肝静脉闭塞病(VOD)的效果.方法:59例急、慢性白血病患者及1例T细胞淋巴瘤患者接受移植治疗.移植患者中3例曾有乙型肝炎病史,1例有轻度脂肪肝病史.移植前所有患者肝功能均正常.采用CyTBI加Ara-C/VP-16或改良BuCy2方案预处理.VOD预防方案:移植前8 d至移植后28 d,采用前列腺素E脂质微球(凯时)30～40vg/d联合小剂量肝素(100U/kg·d-1)及复方丹参30～40 ml/d,发生VOD后继续上述治疗,加用去纤苷10 mg/kg·d-1.结果:59例均获得植入,1例植入失败.2例出现重症VOD,其中1例为接受单倍型半相合外周血干细胞移植的复发ALL患者,1例患者有轻度脂肪肝,接受非血缘外周血干细胞移植.2例均采用较强的清髓性预处理方案,最终死于多脏器功能衰竭.结论:本研究采用的VOD预防方案,VOD发生率低于文献报道,提示前列腺素E脂质微球联合小剂量肝素及复方丹参方案对预防VOD的发生可能有一定效果.     

Comparisons between allogeneic peripheral blood stem cell transplantation and allogeneic bone marrow transplantation in adult hematologic disease: a single center experience

This retrospective study compared the outcomes in 32 adult patients with hematologic diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, severe aplastic anemia) who received allogeneic bone marrow transplantation (BMT, n = 14; median age, 28 years) or allogeneic peripheral blood stem cell transplantation (PBSCT, n = 18; median age, 29 years) from human leukocyte antigen-identical sibling donors. Median follow-up was 58 months in BMT recipients and 18 months in PBSCT recipients. Neutrophil (median, Day 8 vs Day 13, p < 0.001) and platelet engraftment (median, Day 9 vs Day 17, p < 0.001) was faster in the PBSCT group than in the BMT group. Patients receiving PBSCT required less platelet transfusion than those receiving BMT (median, 54 units vs 144 units, p < 0.001), but there was no significant difference in red cell transfusion. At 100 days, there was no difference in the incidence of acute graft-versus-host disease (GVHD) (42.9% vs 33.3%, p = 0.72) or grade II-IV acute GVHD (14.3% vs 5.6%, p = 0.57), and there was no difference in the cumulative incidence of chronic GVHD (20% vs 33.3%, p = 0.67). No chronic GVHD was noted in any relapsed patients (BMT, 5; PBSCT, 3), and no patients with chronic GVHD during follow-up had a relapse. Relapse was the most frequent cause of death inboth groups (BMT, 5/9, 55.6%; PBSCT, 3/4, 75%; p = 0.25); all relapses occurred within 1 year after transplantation. Overall survival was significantly better in the PBSCT group (35.7% vs 77.8%, p = 0.029), but this difference was lost if only hematologic malignancies were analyzed (30.8% vs 63.6%, p = 0.20). Our results are similar to those reported previously, with faster neutrophil and platelet engraftment and less severe acute GVHD and extensive chronic GVHD with PBSCT. Allogeneic PBSCT is a feasible and beneficial alternative to allogeneic BMT in adult hematologic disease.     

Role of pretransplant interferon-alpha(IFN) treatment in the outcome of stem cell transplantation (SCT) from related donors in chronic myelogenous leukemia (CML): results from three Turkish transplant centers

Since transplantation cannot be performed immediately after the diagnosis of chronic myelogenous leukemia (CML), interferon treatment is usually required. This study aims to analyze the effects of interferon-alpha (IFN) treatment on allogeneic stem cell transplantation (SCT) outcome. A total of 106 patients aged 16-47 years and transplanted from HLA-identical sibling donors for CML in chronic phase (CP) were evaluated. In all, 48 had received IFN-alpha for a median duration of 5 months (1-18 months) until a median of 1 month prior to transplantation. Of the patients, 50 have received bone marrow transplant (BMT) whereas 56 have received peripheral blood stem cells (PBSCT) between 1991 and 1999 in three major transplant centers in Turkey. Patient characteristics in both groups were similar. More hematological responders were present in the IFN(+) patients (P=0.0001). No difference was found in engraftment kinetics. The incidences of acute or chronic graft-versus-host disease (GVHD), relapse and graft failure were similar in all patients regardless of stem cell source. Overall survival (OS) and disease-free survival (DFS) at 2 years were similar for both IFN(+) or (-) patients following SCT. With multivariate analysis, pretransplant IFN-alpha use, stem cell source, transplant year and CD34+ cell content were not found to be risk factors for OS. In conclusion, prior IFN exposure did not impair BMT or PBSCT outcome.     

Outcome of transplantation of highly purified peripheral blood CD34+ cells with T-cell add-back compared with unmanipulated bone marrow or peripheral blood stem cells from HLA-identical sibling donors in patients with first chronic phase chronic myeloid leukemia

Outcomes of highly purified CD34(+) peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (CML) (n = 32) were compared with those of PBSCT (n = 19) and of bone marrow transplantation (BMT) (n = 22) in the HLA-compatible sibling donor setting. Median follow-up was 18 months after CD34(+)-PBSCT and unmanipulated PBSCT and 20 months after BMT. CD34(+)-PBSCT was associated with delayed T-cell immune reconstitution at 3 months and 12 months after transplantation compared with PBSCT (P <.001) or BMT (not significant [NS]). The estimated probability of grades II to IV acute graft-versus-host disease (GVHD) was 60% +/- 13% for the PBSCT group, 37% +/- 13% for the BMT group, and only 14% +/- 8% for the CD34(+)-PBSCT group (CD34-PBSCT versus BMT, P <.01; and CD34-PBSCT versus PBSCT, P <.001). The probabilities for molecular relapse were 88% for CD34(+)-PBSCT, 55% after BMT, and 37% after PBSCT (CD34(+)-PBSCT versus PBSCT, P <.03). Cytogenetic relapse probability was 58% after CD34(+)-PBSCT, 42% after BMT, and 28% after PBSCT (NS). After CD34(+)-PBSCT, 26 of 32 patients received a T-cell add-back. Hematologic relapse occurred in 4 of 22 patients after BMT, in 3 of 19 patients after PBSCT, and in only 1 of 32 patients after CD34(+)-PBSCT. The occurrence of a hematologic relapse in patients receiving CD34(+)-PBSC transplants was prevented by donor leukocyte infusions, which were applied at a median of 4 times (range, 1-7 times) with a median T-cell dose of 3.3 x 10(6) x kg/body weight [at a median] beginning at day 120 (range, 60-690 days). The estimated probability of 3-year survival after transplantation was 90% in the CD34(+)-PBSCT group, 68% in the PBSCT group, and 63% in the BMT group (CD34-PBSCT versus BMT, P <.01; and CD34-PBSCT versus PBSCT, P <.03). Transplantation of CD34(+)-PBSCs with T-cell add-back for patients with CML in first chronic phase seems to be safe and is an encouraging alternative transplant procedure to BMT or PBSCT.     

Feasibility and safety of peripheral blood stem cell transplantation from unrelated donors: results of a single-center study

We compared the outcomes in patients receiving unrelated peripheral blood stem cell transplants (PBSCT) with those receiving bone marrow transplants (BMT) in a matched pair analysis. Seventy-four patients with hematological malignancies with HLA-matched (77%) and mismatched (23%) donors were analyzed in this study. Thirty-four patients (45%) were considered as high risk patients. Sixty-eight patients received standard conditioning regimens with Bu/Cy or TBI/Cy. Six patients received an intensified conditioning regimen with the addition of etoposide, thiotepa or melphalan. GVHD prophylaxis consisted of prednisolone, cyclosporine and methotrexate. Groups were matched for patient, donor, transplant characteristics and HLA compatibility. Peripheral blood stem cell collection led to the collection of a higher number of CD34+ and CD3+ cells in comparison to bone marrow collection. Leukocyte engraftment in the PBSCT group occurred in 14 days (median; range 6-26 days) and in the BMT group in 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly. The incidence of grades II-lV acute GVHD in the group of HLA-identical patients was 35% in the PBSCT group and 25% in the BMT group (P < 0.33, log-rank). However, there was a significant difference (P < 0.05, log-rank) in incidence and time to onset of acute GVHD II-IV comparing all patients, including the 17 mismatched transplants. Disease-free survival was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days for PBSC and BMT transplants, respectively. In conclusion, our results indicate that allogeneic PBSCT led to significantly faster leukocyte engraftment but is associated with a higher incidence and more rapid onset of severe acute GVHD comparing all patients, including the 17 mismatched transplants. However, the incidence of severe acute GVHD in HLA-identical patients was not different between the PBSCT and BMT groups.     

Analysis of immune reconstitution in children undergoing cord blood transplantation

OBJECTIVE: The aim of this study was to investigate and compare immune reconstitution in allogeneic cord blood transplantation (CBT) and bone marrow transplantation (BMT) recipients. MATERIALS AND METHODS: Twenty-three children underwent CBT from either human leukocyte antigen-identical siblings (11 cases) or unrelated donors (12 cases) were enrolled in the study, together with 23 matched children receiving BMT. Patients were analyzed 2-3 and 12-15 months after transplant. Recovery of T-, B-, and NK-lymphocyte subsets, proliferative in vitro response to mitogens, as well as cytotoxic activities, were investigated. RESULTS: CBT recipients showed a marked increase in the number of B lymphocytes as compared with patients who underwent BMT (p < 0.001). The absolute number of CD3(+) and CD8(+) T cells, as well as the proliferative response to T-cell mitogens, recovered with time after transplantation, irrespective of the source of stem cells used. Recipients of unrelated CBT had a better recovery of CD4(+) T lymphocytes (p < 0.01). Among patients experiencing acute graft-versus-host disease (GVHD), children given CBT had a much greater production of CD4(+) CD45RA(+) T cells than BMT recipients (p < 0.005). Recovery of NK cell number and innate cytotoxic activities was fast, irrespective of the source of stem cells used. CONCLUSIONS: Despite the much lower number of lymphocytes transferred with the graft, recovery of lymphocyte number and function toward normal in CBT recipients was rapid and comparable to that observed after transplantation of bone marrow progenitors. This prompt immune recovery possibly was favored by the reduced incidence and severity of GVHD observed in children who underwent CBT.     

Quality of life in Thai patients after bone marrow and peripheral blood stem cell transplantation: a comparison study with patients treated with conventional chemotherapy

This study of adult patients of Thai cultural background compared the quality of life (QOL) of patients undergoing bone marrow and peripheral blood stem cell transplantation (BMT/PBSCT) with that of patients treated with conventional chemotherapy (CT). The study population comprised 59 patients who were transplant recipients (29 allogeneic, 29 autograft, and one syngeneic BMT/PBSCT) and 24 patients treated with CT for various hematologic malignancies. The participants completed a 50-item structured QOL questionnaire sent by mail. No significant differences were found between the two patient groups regarding their psychological, social, and treatment-related well-being or their overall QOL; all scores were above 75% of the total. The mean score regarding the physical domain, however, was significantly lower in BMT/PBSCT patients. Areas of highest concern in both groups were sexuality and financial burden. Happiness, functional ability, financial burden, and the degree of familial acceptance were the most important predictors of the self-rated QOL in BMT/PBSCT patients. Seventy-five percent of BMT/PBSCT patients would be willing to undergo the procedure again under the same circumstances. These results indicated that the QOL of Thai patients undergoing BMT/PBSCT was in general satisfactory and comparable to patients treated with conventional CT.     

Allogeneic bone marrow transplantation compared to peripheral blood stem cell transplantation for the treatment of hematologic malignancies: a meta-analysis based on time-to-event data from randomized controlled trials

Controversy remains regarding the transplant outcomes of human leukocyte antigen-identical related bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) for the treatment of patients with hematological malignancies. To provide an estimate of the effect of BMT and PBSCT on clinical outcomes in patients with hematological malignancies, we conducted a meta-analysis based on time-to-event data from 17 randomized controlled trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), from 1972 through July 2010, and conference proceedings through July 2009 and reference lists, without any language restriction, of randomized trials that compared the transplant outcomes after BMT and PBSCT in patients with hematological malignancies were searched for details. Two independent reviewers extracted the data. The outcomes examined were engraftment, graft-versus-host disease (GVHD), relapse, transplant-related mortality (TRM), leukemia-free-survival (LFS), and overall survival (OS). Compared to PBSCT, BMT had lower neutrophil (HR, 2.08; 95% CI, 1.80 to 2.42; p < 0.00001) and platelet (HR, 2.77; 95% CI, 1.78 to 4.30; p < 0.00001) engraftment. BMT was associated with a significant decrease in the development of grades II–IV (HR, 0.75; 95% CI, 0.63 to 0.90; p = 0.002) and III–IV (HR, 0.63; 95% CI, 0.47 to 0.84; p = 0.001) acute GVHD as well as overall (HR, 0.70; 95% CI, 0.59 to 0.83; p < 0.0001) and extensive (HR, 0.60; 95% CI, 0.39 to 0.91; p = 0.002) chronic GVHD. BMT was associated with a higher incidence of relapse (HR, 1.91; 95% CI, 1.34 to 2.74; p = 0.0004). Comparable TRM (1.08; 95% CI, 0.56 to 2.10; p = 0.81), LFS (HR, 1.04; 95% CI, 0.83 to 1.30; p = 0.73), and OS (HR, 1.06; 95% CI, 0.81 to 1.39; p = 0.65) were demonstrated for both treatments. An inverse linear relationship was observed between the acute GVHD difference (PBSCT minus BMT) and the outcome of OS (p = 0.016). Our meta-analysis suggest that BMT leads to slower hematological recovery, increasing rates of relapse, and a lower risk of GVHD, but no significant difference in LFS and OS. A lower incidence of acute GVHD is associated with a superior OS.     

Allogeneic bone marrow vs. peripheral blood stem cell transplantation: a long-term retrospective single-center analysis in 329 patients

Objectives: Granulocyte colony‐stimulating factor‐mobilized peripheral blood hematopoietic stem cell transplantation (HSCT) provides a valuable and increasingly used alternative to bone marrow transplantation (BMT). This retrospective study aimed at determining whether the stem cell source is predictive for outcome, relapse incidence, non‐relapse mortality, and severity and incidence of both, acute and chronic graft‐versus‐host disease (GVHD) in patients undergoing allogeneic HSCT. Patients and methods: Between 1983 and 2007, 329 adult patients (median age 40, range 18–76) received a first allogeneic HSCT from either sibling (n = 203) or volunteer unrelated donors (n = 126) at our institution. The source of stem cells was bone marrow in 177 (54%) and peripheral blood in the remaining 152 (46%) patients. Results: Overall survival was 37% (31–43%, 95% confidence interval, CI), the relapse incidence was 30% (25–36%, 95% CI), and the non‐relapse mortality was 43% (38–49%, 95% CI) for the entire cohort with no significant differences between peripheral blood stem cell or BMT. In patients receiving myeloablative conditioning, peripheral blood stem cell transplantation (PBSCT) was associated with a significantly lower non‐relapse mortality (32% vs. 46%, P = 0.05), which, however, was restricted to standard‐risk disease (23% vs. 42%, P = 0.02). The overall cumulative incidences of acute GVHD II–IV were 51% and 54% following bone marrow and PBSCT, respectively. Severe acute GVHD III–IV was significantly more frequent after BMT (24% vs. 14%, P = 0.04), whereas chronic GVHD was significantly more frequent following PBSCT (48% vs. 24%, P = 0.0001). By multivariate analysis, PBSCT was only predictive for chronic GVHD (RR 2.29, P = 0.02). Conclusion: Although we failed to demonstrate any advantage of PBSCT over conventional BMT with regard to overall survival, relapse incidence and non‐relapse mortality PBSCT were associated with a significantly higher incidence of chronic graft‐versus‐host disease. Therefore, and by virtue of observations, that some patient groups might benefit from either stem cell source, there is still need for prospective randomized trials with special emphasize on quality of life in long‐term survivors.     

Impact of cytomegalovirus serostatus on outcome of unrelated cord blood transplantation for adults: a single-institute experience in Japan

Cytomegalovirus (CMV) disease is one of the major infectious complications after allogeneic hematopoietic stem cell transplantation (SCT). Several studies have shown that CMV-seropositive patients have a substantial survival disadvantage after bone marrow transplantation (BMT) or peripheral blood SCT (PBSCT). Between August 1998 and February 2006, 101 adult patients underwent myeloablative cord blood transplantation (CBT) from unrelated donors at our institution. Sixteen and 85 patients were CMV-seronegative and CMV-seropositive, respectively, prior to CBT. Outcomes of CBT were compared between CMV-seronegative and CMV-seropositive patients. The cumulative incidences of neutrophil engraftment at 60 d after CBT did not differ between CMV-seronegative and CMV-seropositive patients (100% and 94%, P = 0.09); however, the cumulative incidence of platelet engraftment at 100 d was higher in CMV-seronegative patients than CMV-seropositive patients (100% vs. 86%, P < 0.005). The cumulative incidence of CMV antigenemia at 100 d was lower in CMV-seronegative patients than CMV-seropositive patients (0% vs. 77%, P < 0.001); however, the cumulative incidences of CMV disease did not differ between CMV-seronegative and CMV-seropositive patients (0% vs. 1%, P = 0.84). The probabilities of disease-free survival at 2 yr also did not differ between CMV-seronegative and CMV-seropositive patients (92% vs. 72%, P = 0.16). The outcomes of CBT for CMV-seropositive patients as well as CMV-seronegative patients in our series were favorable. This might be due to effective antiviral therapy for CMV infection. Large-scale studies are needed to determine the impact of recipient CMV serostatus on the outcome of CBT for adults.     

Immature platelet fraction for prediction of platelet engraftment after allogeneic stem cell transplantation

Platelet regeneration represents an important and separate element in the engraftment process for allogeneic stem cell transplantation. Fully automated flow cytometry using blood cell counters now allows reliable quantification of reticulated platelets, expressed as the immature platelet fraction (IPF). We studied the kinetics of IPF in six patients grafted with allogeneic peripheral blood stem cell transplantation (PBSCT), 12 patients with bone marrow transplantation (BMT) and seven patients with cord blood transplantation (CBT). Preconditioning therapy caused an immediate and rapid fall in tri-lineage hematopoiesis. IPF rose transiently above 3% after a mean duration of 11 days post-PBSCT, 18 days post-BMT and 19 days post-CBT. This was 1, 4 and 13 days earlier than platelet engraftment, respectively. A linear correlation model showed a close association between the rise of IPF and tri-lineage engraftment after transplantation. IPF counting may thus provide an accessible measure of thrombopoietic activity, leading to early evaluation of marrow function and allowing monitoring of platelet regeneration.     

Reduced-intensity stem cell transplantation using allogeneic peripheral blood stem cells from the same donor for relapsed leukemia after bone marrow transplantation

We report the clinical courses of two cases with relapsed acute lymphoblastic leukemia (ALL) after allogeneic bone marrow transplantation (BMT). After reinduction chemotherapy, the patients received reduced-intensity stem cell transplantation using allogeneic peripheral blood stem cells harvested from their previous BMT donors. The conditioning regimen used consisted of fludarabine and melphalan. Graft-versus-host disease (GVHD) prophylaxis was performed with low dose cyclosporin A (CsA, 1 mg/kg/day d.i.v.) on its own. The regimen related toxicity was minimal, and stable engraftment was achieved. Since acute GVHD had not developed by day 30, CsA was stopped abruptly in both cases. After CsA withdrawal, acute GVHD developed, and subsequent chronic GVHD. One of two cases is alive without any relapse of the leukemia 40 months after the peripheral blood stem cell transplantation (PBSCT). In the other case, ALL relapsed 15 months after the PBSCT, however, complete remission was again induced concomitantly with reactivated GVHD. In both these cases, the results suggest that using PBSC as a stem cell source and abrupt cessation of GVHD prophylaxis provided a potent graft-versus-leukemia effect.     

Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin.

Transplant-related mortality (TRM) following allo- geneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin <0.9 and/or BUN <21) and 93 patients with score 2 (high risk) (bilirubin >/=0.9 and BUN >/=21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P < 0.01), after adjustment for year of transplant (P < 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be eligible for programs designed to intensify prophylaxis of post-transplant complications.     

Allogeneic transplantation of G-CSF mobilized peripheral blood stem cells from unrelated donors: a retrospective analysis

BACKGROUND AND OBJECTIVES: Allogeneic peripheral blood stem cell transplantation (PBSCT) from matched siblings has lead to clinical results comparable to those of standard bone marrow transplantation (BMT). We report the outcome of 79 patients transplanted with PBSC from unrelated donors. DESIGN AND METHODS: In 61 cases PBSC were used for primary transplantation whereas 18 patients were treated for relapse or graft-failure. In 35 patients receiving primary transplants, T-cell depletion (TCD) using CD34 positive selection of PBSC with or without additional T-cell depletion had been performed to reduce the risk of graft-versus-host-disease (GvHD). RESULTS: The rate of primary graft-failure was higher (20%) in the TCD group than in that receiving unmanipulated grafts (UM) (5%, p=0.007). Patients with standard risk (n=34) receiving first transplants had a significantly better overall (60.4% vs. 24%, p=0.02) and disease-free survival (57.2% vs. 22.3%, p=0.006) compared to a high risk group of patients (n=21). There were no differences in the speed of neutrophil and platelet engraftment between TCD and UM transplants. As expected, the cumulative risk for acute GvHD grade II.-IV was significantly higher in the patients who had received UM grafts (71.8% vs. 38.1%, p=0.005). Although a trend towards a better survival rate was observed after TCD transplantation (52.2%) compared to the UM group (38.1%), this difference was not statistically significant. The probability of relapse was significantly higher in patients after UM transplants (38.8% vs. 8. 4%). This apparent paradox is explained by the higher number of high-risk patients in this group (p=0.03). Multivariable analysis of disease-free survival revealed risk category (p=0.02) and use of ATG (p=0.03) to be of significant impact. All patients (n=6) with non-malignant diseases are alive with full donor chimerism. INTERPRETATION AND CONCLUSIONS: These data show that PBSC from unrelated donors can be transplanted either unmanipulated or CD34 selected. Prospective studies comparing BMT with PBSCT from unrelated donors are needed in defined disease categories.