Serum elastase and antithrombin-3 levels after umbilical cord blood transplantation or bone marrow transplantation

The severity of graft-versus-host disease (GVHD) was compared after cord blood transplantation (CBT) and bone marrow transplantation (BMT). The severity of GVHD was also analyzed in relation to serum elastase and antithrombin-3 (AT-3) levels. There was no significant difference in the average grade of acute GVHD between 49 BMT patients and 20 CBT patients (X²-test). However, there was a lower incidence of patients without acute GVHD (grade 0) or patients with severe acute GVHD (grade 3 or 4) in CBT compared with BMT group. Linear regression analysis found no significant correlation between the serum elastase level and the grade of acute GVHD, between the serum AT-3 level and the grade of acute GVHD, or between the serum levels of elastase and AT-3 before conditioning and after engraftment. The AT-3 level after engraftment was significantly higher in the CBT group than in the BMT group and it did not fail along with the elevation of elastase in the CBT group (p < 0.01 by the Mann–Whitney U-test vs. the BMT group). In conclusion, the lower risk of severe acute GVHD in the CBT group may have been related to the smaller decrease of AT-3 after transplantation.     

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.     

Clinical and economic comparison of allogeneic peripheral blood progenitor cell and bone marrow transplantation for acute lymphoblastic leukemia in children

There is limited experience in the use of peripheral blood progenitor cells (PBPC) for allogeneic transplantation in children. In the present study we compared engraftment kinetics, incidence of acute and chronic graft-versus-host disease (GVHD) and the outcome and economic costs of allogeneic PBPCT vs BMT in children with ALL in a single institution. All children were transplanted in complete remission (CR) with a similar conditioning regimen and the same GVHD prophylaxis. Patients undergoing PBPCT achieved myeloid and platelet engraftment before patients undergoing BMT (P < 0.001). Platelet recovery was faster for the PBPCT group (P < 0.014 for 50 x 10(9)/l and P < 0.039 for 100 x 10(9)/l). Incidence and severity of acute and chronic GVHD were similar in both groups (acute grade 1-2: 9/13 for PBPCT vs 9/11 for BMT; chronic GVHD: 5/12 for PBPCT vs 3/8 for BMT). Hospital stay was shorter for the PBPCT than for the BMT group (28.8 days vs 42.9 days, respectively) and the PBPCT group used less clinical resources, resulting in overall lower cost for PBPCT (US $14,046) compared to BMT (US $19,840). There was no statistically significant difference in DFS between PBPCT and BMT (68.4% vs 50%, respectively).     

Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation

Haemorrhagic cystitis (HC) is an important complication after bone marrow transplantation (BMT). Overt HC (grade > or =2, gross haematuria, clot retention and impairment of renal function), clinically more important than mild and occult HC (grade 1, microscopic haematuria), leads to substantial morbidity and occasional mortality. We retrospectively analyzed 32 cases of clinically overt HC from a series of 236 BMT patients. Significant risk factors included the use of busulphan during conditioning, allogeneic BMT and acute GVHD. Logistic regression showed GVHD to be the most important risk factor. According to the time of engraftment, HC could be divided into pre- and post-engraftment subtypes. Pre-engraftment HC was brief, not more severe than grade 2, and subsided with supportive treatment. In contrast, post-engraftment HC was protracted, often of grade > or =3, associated with severe GVHD, and required surgical intervention in many cases. Polyoma BK viruria, but not adenoviruria, could be demonstrated in both types of HC. The increased severity and association with GVHD of post-engraftment HC suggested that attack of urothelium by immunocompetent cells, possibly directed against BK viral antigens, might play a pathogenetic role.     

Successful neutrophil engraftment by reduced use of granulocyte colony-stimulating factor after allogeneic hematopoietic stem cell transplantation with mycophenolate mofetil for graft-versus-host disease prophylaxis

In allogeneic hematopoietic stem cell transplantation (allo-SCT), most physicians in Japan utilize granulocyte colony-stimulating factor (G-CSF) at a high dose (HD) of 300 μg/m(2) per day for filgrastim to promote faster neutrophil engraftment. However, the necessity of the HD has not been validated under graft-versus-host disease (GVHD) prophylaxis by mycophenolate mofetil (MMF), which can also be expected to facilitate engraftment. In a total of 51 patients, we compared the clinical outcomes between a standard dose (SD) fixed at 300 μg per day and a HD of G-CSF. While time to neutrophil engraftment was not different in the HD and SD groups in patients receiving cord blood transplantation (CBT, 20 vs. 17.5 days, P = 0.243) or bone marrow transplantation (BMT, 11 vs. 10 days, P = 0.227), there seemed to be an increased risk of developing acute GVHD in the HD group with CBT (20 vs. 0%, P = 0.073) and BMT (57 vs. 24%, P = 0.165). Progression-free survival of patients in the HD group was likely to be worse compared with that of the SD group with CBT (P = 0.099). In this study, the clinical benefits of a HD of G-CSF could not be documented, and we find that the use of G-CSF at a SD after allo-SCT with MMF should be prospectively evaluated.     

Serum IgE levels after bone marrow transplantation

Total serum IgE levels were followed in 135 bone marrow transplant recipients in order to determine the clinical significance of post-transplant serum IgE monitoring. Patients with IgE levels less than 60 U/ml at the time of bone marrow transplantation (BMT) (59%) experienced at least one IgE peak. Patients with pretransplant IgE levels greater than or equal to 60 U/ml (16%) showed decreasing values following BMT. In 19% of patients, IgE levels were low and did not change up to 3 months after BMT. Increase in IgE levels coincided in time with engraftment (p less than 0.01) and acute graft-versus-host disease (GVHD) (p less than 0.01). Early IgE peaks were also seen in patients without GVHD. Maximal IgE values did not differ during grades II-IV GVHD compared with grades 0-1, but two or more peaks were more common in patients with grades II-IV (p less than 0.001). IgE peaks also appeared in patients receiving T cell-depleted marrow without GVHD. Syngeneic bone marrow recipients had high IgE levels after BMT. Two patients had increasing IgE values following reconditioning and retransplantation, but booster grafts had no effect on IgE levels. IgE levels were not changed during septicemia, herpes simplex virus or cytomegalovirus infections, and chronic GVHD. No linear correlation was found between serum IgE levels and CD4+/CD8+ ratios, percentages, or absolute numbers of either group of cells. It was concluded that serum IgE elevation is found in association with engraftment and acute GVHD, but is mainly caused by the conditioning treatment.     

Retrospective comparison of CD34-selected allogeneic peripheral blood stem cell transplantation followed by CD8-depleted donor lymphocyte infusions with unmanipulated bone marrow transplantation

We have previously reported the feasibility of allogeneic CD34-selected PBSC transplantation followed by pre-emptive CD8-depleted DLI (study group). In this report, we retrospectively compare the clinical outcome of the 24 patients included in this study with an historical group of 35 patients receiving unmanipulated marrow (BMT group). Patients in the study group had significantly faster neutrophil and platelet recovery and were discharged earlier than BMT patients. The actuarial 150-day (after DLI) probability of developing grade II-IV acute GVHD was 28% for the study group versus 62% for the BMT group (p=0.002). The actuarial 2-year probability of developing chronic GVHD was similar (37 versus 36% (NS)) but chronic GVHD was significantly delayed in the study group (p=0.003). The actuarial 2-year probability of relapse was 30% in the study group versus 33% in the BMT group (NS). The actuarial 2-year probability of survival was 45% in the study group versus 43% in the BMT group (NS). We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to confirm these results.     

Treatment of hematological malignancies with nonmyeloablative, HLA-haploidentical bone marrow transplantation and high dose, post-transplantation cyclophosphamide

Hematopoietic stem cell transplantation provides the only potential curative option in many patients with hematological malignancies. Finding a suitably matched donor in a timely manner is often difficult. However, most patients have a partially HLA-mismatched (HLA-haploidentical) first-degree relative readily available. Historically, HLA-haploidentical bone marrow transplantation (BMT) has been considered extremely high risk due to high rates of life-threatening graft-versus-host disease (GVHD) and non-relapse mortality (NRM). Modifications of the stem cell graft, such as T-cell depletion, have resulted in poor rates of engraftment. We have recently completed a phase II clinical trial of nonmyeloablative HLA-haploidentical hematopoietic BMT followed by post-transplantation high-cyclophosphamide. High-dose cyclophosphamide has been shown to create immunogenic tolerance by specifically killing activated mature T-cells. As a result, alloreactive T-cells in the donor graft are selectively destroyed thereby decreasing the incidence of severe GVHD. As well, host-versus-graft reactive T-cells are also selectively eliminated thereby increasing rates of engraftment. Among 210 patients with hematological malignancies receiving nonmyeloablative, HLA-haploidentical BMT with post-transplantation cyclophosphamide, the rate of sustained donor cell engraftment has been 87%. The cumulative incidence of grade 2-4 acute GVHD is 27%, grade 3-4 acute GVHD is 5% and chronic GVHD is 15%. Interestingly, increasing HLA disparity between donor and recipient was not associated with increasing incidence of GVHD or decreased event-free survival. Nonmyeloablative haploidentical stem cell transplantation with post-transplantation cyclophosphamide seems to be a promising, potentially curative, option for patients with hematological malignancies who either lack an HLA-matched related or unrelated donor, or in whom a myeloablative preparative regimen is contraindicated due to significant co-morbidities or history of extensive pre-treatment.     

Unmanipulated HLA 2-3 antigen-mismatched (haploidentical) bone marrow transplantation using only pharmacological GVHD prophylaxis

OBJECTIVE: The incidence of severe graft-vs-host disease (GVHD) in unmanipulated human leukocyte antigen (HLA) 2-3 antigen-mismatched bone marrow transplantation (BMT) using cyclosporine and methotrexate as GVHD prophylaxis is 80% to 90%. We investigated whether pharmacological GVHD prophylaxis consisting of four drugs, including a steroid, effectively suppressed GVHD in this transplantation setting. MATERIALS AND METHODS: Thirty patients who had hematologic malignancies at an advanced stage or with poor prognosis underwent allogeneic BMT using a myeloablative preconditioning regimen consisting of cyclophosphamide (60 mg/kg x 2), total body irradiation (8-10 Gy), and fludarabine (30 mg/m(2) x 4) with or without cytosine arabinoside (2 g/m(2) x 4), and GVHD prophylaxis consisting of a combination of tacrolimus, methotrexate, mycophenolate mofetil, and methylprednisone (2 mg/kg). Early therapeutic intervention for GVH reaction or grade I GVHD was performed, and steroid was slowly tapered. RESULTS: All patients achieved donor-type engraftment. Neutrophil (>0.5 x 10(9)/L) and platelet (>20 x 10(9)/L) engraftment was achieved on day 13 and on day 30, respectively. Seventeen patients (56.7%) had no GVHD. Eleven patients (36.7%) developed grade II-III acute GVHD. Seven patients (23.3%) died of transplant-related toxicity, including fungal or viral infections and thrombotic microangiopathy, and four patients died of disease progression. Estimated relapse rate at 3 years was only 20.9%. The probability of survival at 3 years was 49.9%. CONCLUSIONS: These data suggest that, in unmanipulated HLA-haploidentical allogeneic BMT, this GVHD prophylactic regimen, which includes methylprednisolone 2 mg/kg, and early therapeutic intervention for GVH reaction suppress the incidence of severe GVHD to an acceptable level, while preserving the graft-vs-leukemia effect.     

Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease

Allogeneic bone marrow transplantation (BMT) from HLA-identical siblings is an accepted treatment for both thalassemia and sickle cell disease (SCD). However, it is associated with decided risk of both transplant-related mortality (TRM) and chronic graft-versus-host disease (GVHD). We analyzed 44 patients (median age, 5 years; range, 1-20 years) given an allogeneic related cord blood transplant for either thalassemia (n = 33) or SCD (n = 11). Thirty children were given cyclosporin A (CsA) alone as GVHD prophylaxis, 10 received CsA and methotrexate (MTX), and 4 patients received other combinations of immunosuppressive drugs. The median number of nucleated cells infused was 4.0 x 10(7)/kg (range, 1.2-10 x 10(7)/kg). No patient died and 36 of 44 children remain free of disease, with a median follow-up of 24 months (range, 4-76 months). Only one patient with SCD did not have sustained donor engraftment as compared with 7 of the 33 patients with thalassemia. Three of these 8 patients had sustained donor engraftment after BMT from the same donor. Four patients experienced grade 2 acute GVHD; only 2 of the 36 patients at risk developed limited chronic GVHD. The 2-year probability of event-free survival is 79% and 90% for patients with thalassemia and SCD, respectively. Use of MTX for GVHD prophylaxis was associated with a greater risk of treatment failure. Related CBT for hemoglobinopathies offers a good probability of success and is associated with a low risk of GVHD. Optimization of transplantation strategies could further improve these results.     

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing GVHD and rejection of organ transplants. As the fludarabine-based conditioning regimens without total body irradiation have been reported to be promising for bone marrow transplantation (BMT) from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated BMT. Five patients underwent BMT with cyclophosphamide (50 mg/kg once daily i.v. on days -9, -8, -7 and -6), fludarabine (30 mg/m2 once daily i.v. on days -5, -4, -3 and -2) and thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2 and -1) from HLA-matched unrelated donors. Complete donor type hematologic recovery was achieved in all patients. No serious complication occurred during BMT. Only one patient developed grade I acute GVHD resolved spontaneously. Except for one who had rupture of hepatic adenoma 78 days after BMT, all the other four patients are still alive with median 566 days. Fludarabine, cyclophosphamide plus thymoglobulin conditioning allows for the promising results of good engraftment, tolerable toxicity and minimal GVHD.     

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.     

Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen.

We studied the clinical outcomes of 171 adults with hematologic malignancies who received unrelated cord blood transplantation (CBT) as a primary unrelated stem-cell source (n=100), or bone marrow transplant (BMT) or peripheral blood stem-cell transplant (PBSCT) from related donors (n=71, 55 BMT and 16 PBSCT). All patients received myeloablative regimens including 12 Gy total body irradiation. We analyzed the hematologic recovery, and risks of graft-versus-host disease (GVHD), transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. Significant delays in engraftment occurred after cord blood transplantation; however, overall engraftment rates were almost the same for both grafts. The cumulative incidences of grades III to IV acute and extensive-type chronic GVHDs among CBT recipients were significantly lower than those among BMT/PBSCT recipients. Multivariate analysis demonstrated no apparent differences in TRM (9% in CBT and 13% in BMT/PBSCT recipients), relapse (17% in CBT and 26% in BMT/PBSCT recipients), and DFS (70% in CBT and 60% in BMT/PBSCT recipients) between both groups. These data suggest that unrelated cord blood could be as safe and effective a stem-cell source as related bone marrow or mobilized peripheral blood for adult patients when it is used as a primary unrelated stem-cell source.     

Allogeneic bone marrow transplantation using partially-matched related donors

Six patients with advanced leukemia and one with severe combined immunodeficiency syndrome received allogeneic bone marrow transplantation (BMT) from HLA haploidentical donors who were compatible for one or two loci on the non-shared chromosome. Methotrexate was used for prophylaxis against acute graft-versus-host disease (GVHD). All patients engrafted but developed moderate to severe acute GVHD, and three patients died. Two leukemic patients relapsed but two others survived and were free of disease 403 and 936 days post-transplant. BMT using related partially matched donors may result in durable engraftment and long-term survivors. The implications of using such donors in expanding the application of BMT are discussed.     

Outcome of adult severe or very severe aplastic anemia treated with immunosuppressive therapy compared with bone marrow transplantation: multicenter trial

To compare survival rates and long-term complications after bone marrow transplantation (BMT) or treatment with immunosuppressive agents (ISA) in the management of adult aplastic anemia (AA) and to identify prognostic factors associated with improved survival, we evaluated 229 adult AA patients treated with ISA from 1990 to 2001 and compared the results with those for 64 BMT recipients. Of 156 patients with severe aplastic anemia (SAA) or very severe AA treated with ISA (antithymocyte globulin [ATG] or ATG plus cyclosporine), 46.8% showed complete or partial response and 7.1% had relapses. After long-term follow-up, 1 case each of acute leukemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria developed. The 6-year survival rate was 69%. Response to ISA, disease severity, and low absolute neutrophil count (ANC) (< or = 200/mm3) were associated with poor survival. Patient age, sex, initial platelet count, etiology, or treatment regimen did not significantly affect survival. Cox regression analysis showed low ANC to be the only pretreatment variable significantly associated with poor survival (P = .000). Of 64 BMT recipients, 82.8% had sustained engraftment, and 12.5% experienced graft failure. Twenty (31.3%) of the patients developed grade II to IV acute graft-versus-host disease (GVHD), and 12 (18.8%) of the patients developed chronic GVHD. The 6-year survival rate was 79%. Patient age and sex, disease severity, etiology, ANC, initial platelet count, and treatment regimen did not affect survival. Survival of 83 AA patients, aged 14 to 40 years, treated with ISA was not statistically significant from that of 61 adult AA patients who underwent BMT (6-year survival rate, 65% and 79%, respectively). However, BMT in adult AA achieved long-term engraftment and a lower relapse rate than ISA. These results suggest that ISA can achieve a high response rate and long-term survival among patients with adult AA, regardless of disease severity. Further studies with larger numbers of patients and long-term follow-up are needed.     

Successful bone marrow transplantation in children with severe aplastic anemia using HLA-partially matched family donors

Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25–30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long-lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor. © 1993 Wiley-Liss, Inc.     

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).     

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.     

Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial

A randomized trial was carried out comparing cyclosporin A (CsA) and short-term methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups received CsA orally, with gradual drug reduction until discontinuation 8 to 12 months after BMT. Patients randomized in both arms had comparable characteristics and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrophil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA alone group, respectively (P =.01). No significant difference was observed in the probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation-related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT, the 5-year survival probability is 94% for patients in the CsA/MTX group and 78% for those in the CsA alone group (P =. 05). These data indicate that the use of CsA with MTX is associated with improved survival in patients with SAA who receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)     

Retrospective Comparison of CD34-selected Allogeneic Peripheral Blood Stem Cell Transplantation Followed by CD8-depleted Donor Lymphocyte Infusions with Unmanipulated Bone Marrow Transplantation

We have previously reported the feasibility of allogeneic CD34-selected PBSC transplantation followed by pre-emptive CD8-depleted DLI (study group). In this report, we retrospectively compare the clinical outcome of the 24 patients included in this study with an historical group of 35 patients receiving unmanipulated marrow (BMT group). Patients in the study group had significantly faster neutrophil and platelet recovery and were discharged earlier than BMT patients. The actuarial 150-day (after DLI) probability of developing grade II-IV acute GVHD was 28% for the study group versus 62% for the BMT group (p=0.002). The actuarial 2-year probability of developing chronic GVHD was similar (37 versus 36% (NS)) but chronic GVHD was significantly delayed in the study group (p=0.003). The actuarial 2-year probability of relapse was 30% in the study group versus 33% in the BMT group (NS). The actuarial 2-year probability of survival was 45% in the study group versus 43% in the BMT group (NS). We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to confirm these results.