anti-ABO Antibodies Research Articles

Successful Use of Anti-CD20 Monoclonal Antibody (Rituximab) for ABO-Incompatible Living-Related Liver Transplantation

Humoral rejection after ABO-incompatible liver transplantation often causes graft loss and a life-threatening situation. We used rituximab, which can eliminate B cells highly selectively, as an additional therapy for ABO-incompatible living-related liver transplantation. Patient 1 was a 1-year-old girl with biliary atresia. Her blood type was O, and the donor's was A. She underwent two plasma exchanges before liver transplantation and had triple immunosuppressants (mycophenolate mofetil, tacrolimus, and methylprednisolone). She was diagnosed with humoral rejection by needle biopsy on postoperative day 6. Rituximab was used for 3 days at 375, 187, and 187 mg/m(2) and successfully reduced the antibody titer, transaminase, and CD19(+) cells count in peripheral blood lymphocytes. The patient has not had any severe rejection, infection, or serious complications 2 years posttransplantation. Patient 2 was a 42-year-old woman with primary biliary cirrhosis. The blood type was O, and the donor's was B. She received three plasma exchanges, triple immunosuppressants, splenectomy, intraarterial anticoagulant therapy, and rituximab (375 mg/m(2) immediately after transplantation). The titer and CD19(+) cells count remained persistently low throughout the recovery course. She did not develop humoral rejection 1 year after transplantation. Rituximab efficiently reduces anti-ABO antibody titer by selectively eliminating B cells and is safe and effective against humoral rejection after ABO-incompatible liver transplantation.

Similar Humoral Immunity Parameters in Chronic Lymphocytic Leukemia Patients Independent of VH Gene Mutation Status

Chronic lymphocytic leukemia (CLL) is a clonal B-cell disorder, which has recently been divided into 2 subtypes based on the somatic hypermutation status of the immunoglobulin heavy chain (IgVH) genes. In patients with unmutated tumor cells the survival time is approximately half of that in mutated cases, but the reason for this difference is poorly understood. Since infections are the major cause of mortality in CLL, we investigated the effect of the mutation status on host immunity and proneness to infections in patients with CLL. As expected, the disease progression seemed to be faster and the disease more advanced (Binet B and C) among unmutated patients than in the mutated ones. Surprisingly, no differences in humoral immunity [immunoglobulin G (IgG), IgM, IgA, IgG subclasses, anti-ABO blood group antibodies and mannan-binding lectin (MBL)] or immune responses (Haemophilus influenzae serotype b conjugate vaccination) were detected between these 2 patient groups. Furthermore, UM-patients were not more prone to infections compared to M-patients, and therapy had no impact on the incidence and pattern of infections in either of the patient groups. The current findings within this patient cohort reveal that the worse outcome in the unmutated subgroup is not caused by more severe defects in immunity and increased susceptibility to infections when compared with the hypermutated group. It is thus conceivable that active immunization procedures such as vaccination can successfully be applied on patients with unmutated IgVH gene and advanced disease stage.

Successful Re-Engraftment after Second Allogeneic Transplantation for Graft Failure in Patients with Refractory Hematologic Malignancies.

Graft failure (GF), either primary or after transient engraftment, following matched, related allogeneic hematopoetic stem cell transplantation (HSCT) without T-cell depletion is usually less than 3% for hematological diseases. Graft failure using non-T-cell depleted unrelated donors in chronic myelogenous leukemia (CML) as reported by the national marrow registry is approximately 9.7%. For aplastic anemia, the incidence of graft failure is estimated to be 10%. In this report, we present 3 patients (Pts) with GF following unrelated ablative allogeneic HSCT (two with peripheral blood stem cells and one with bone marrow). Pt. 1 had transient engraftment and Pts 2 & 3 had primary GF. Their relevant demographics are as follows:TABLE 1DiseaseUnrelated DonorAge/SexGVHD: BMT1GVHD: BMT2PTLDPt1CML, 1st Chronic PhaseMatched29/FNoneGrade IIYesPt2MDSMatched57/MNoneNoneNoPt3MDS/AML1ag Mismatched55/MNoneNoneNoAll patients were initially conditioned with alemtuzumab (A) 30mg/day on days −8 to −6, fludarabine (F) 30mg/m2/day on days −7 to −3, and busulfan .8mg/kg x 16 doses (two patients) or x 8 doses (one patient) on days −5 to −2. Conditioning for HSCT #2 included cyclophosphamide 50mg/kg/day, Mesna 50mg/kg/day, and thymoglobulin 2.5mg/kg/day on days −5 to −2. Graft versus host disease (GVHD) prophylaxis included tacrolimus for both HSCT transplants, and low dose methotrexate (3 doses) combined with prednisone (2mg/kg) on days 0–18 followed by a two week taper for HSCT #2. The stem cell product and engraftment kinetics are shown below. [Display omitted] Significant toxicities after HSCT#2 have included successful resolution of PTLD in patient #1 (who also experienced infection with pulmonary respiratory syncitial virus, BK viruria, and fatty infiltration of the liver). BK viruria was noted in patient #2, as well as hypertension and a modest pericardial effusion with global hypokinesis (but with a normal ejection fraction). Hepatomegaly was documented, but no vaso-occlusive disease was established. Patient #3 developed a cardiac arrhythmia, hypertension, and BK viruria and remains Plt transfusion dependent. Patient #1 had grade II GVHD of the skin and gut, but patients 2 and 3 had none. GVHD has been <grade II. GF occurred in 3/17 Pts with MUD transplants that included alemtuzamab in the conditioning regimen. While GF is unacceptably high, it is encouraging that all 3 Pts. successfully completed 2nd MUD transplant with transfusion and cytokine independence using same donor preceded in Pts. 1 & 2 by depletion of anti-ABO incompatible antibodies in the recipient.[table2]

Impact of positive PRA on the results of ABO-incompatible kidney transplantation

Introduction Due to the continuing shortage of cadaveric donors in Japan, ABO-incompatible living kidney transplantation (LKT) is being performed. It is well known that highly sensitized patients with positive panel reactive antibodies (PRA) often present with acute rejection. Therefore, we examined the impact of a positive PRA on the results of ABO-incompatible LKT. Materials and methods One hundred seventy-seven recipients underwent ABO-incompatible LKT between January 1989 and March 2003. Of these patients, 37 who had been examined for PRA before transplantation were included in this study. There were 25 men and 12 women of mean age 37.3 years. Plasmapheresis was performed to remove anti-ABO antibodies before transplantation. During the induction phase, methylprednisolone, azathioprine, or mycophenolate mofetil and cyclosporine or tacrolimus were used for immunosuppression. Splenectomy was performed at the time of kidney transplantation in all patients. PRA was measured using FlowPRA by flow cytometer. Results Eight of the 37 patients had a positive PRA before transplantation (class I, 5; class II, 1; class I and class II, 2). The incidence of acute rejection was 37.9% in the patients with a negative PRA and 37.5% in patients with a positive PRA. One patient with a negative PRA and one patient with a positive PRA lost grafts due to acute rejection. Conclusions Positive PRA may not increase the incidence of acute rejection in ABO-incompatible LKT because plasmapheresis and splenectomy are performed to eliminate anti-ABO antibody.

RELATIONSHIP BETWEEN ANTI-ABO ANTIBODY PRODUCTION AND HEMOLYTIC ANEMIA AFTER MINOR ABO-MISMATCHED LIVING-DONOR LOBAR LUNG TRANSPLANTATION

O481 Aims: To solve the shortage of lung donors, we have performed twenty eight cases of living-donor lobar lung transplantation since October 1998. Although lungs from ABO-identical donors were used if available, in instances when suitable ABO-identical donors were not found, lungs were transplanted from donors showing minor ABO mismatches. It is known that solid organ transplantation from donors with minor ABO mismatches can be complicated by hemolysis. The aim of this study was to evaluate the relationship between anti-ABO antibody production and outcome of lung transplantation performed with ABO-mismatched living-donor lungs. Methods: We reviewed 28 patients (28 recipients with 55 donors) who underwent living-donor lobar lung transplantation between October 1998 and March 2004. In this patient population, thirteen cases (46.4%) were minor ABO-mismatched transplant. Anti-A or B-IgG antibodies (Abs) in the serum and red cell elutes were examined. Results: All of these 28 patients are alive (mean observation period: 23.1 (ranging from 1 to 65) months). Anti-A or B-IgG Abs could be detected in four out of thirteen minor ABO-mismatched patients (30.8%) after transplant, but only one of them (29 year-old woman, bronchiolitis obliterans) had evidence of severe hemolytic anemia due to donor-derived antibodies. The titer of anti-A-IgG Abs in her serum increased to 1:32 on day 26, and her hemoglobin level decreased from 11.6 g/dL to 6.6 g/dL with signs of hemolysis. She required 2800 mL of group O concentrated RBCs. On the other hand, the titer of Abs in other mismatched patients’ serum reached from 1:4 to 1:16 (mean 1:8), and there was no signs of anemia. Anti-ABO antibody production and anemia were not associated with gender, age, relationship between donors and recipients, and HLA matching. The incidence of acute rejection, chronic rejection, and infection was not affected by ABO mismatch. Conclusions: We report thirteen cases of minor ABO-mismatched living-donor lobar lung transplantation. Four of them developed anti-A or B-IgG antibodies in the serum, but only one of them showed hemolytic anemia. The titer of anti-A-IgG Abs of this patient was higher than Abs of others, but the mechanism of the phenomenon is obscure. We conclude that living-donor lobar lung transplantation across ABO mismatches is an acceptable treatment for end-stage lung diseases.

Impact of recipient age on outcome of ABO-incompatible living-donor liver transplantation.

Transplantation of hepatic grafts from ABO-incompatible donors is controversial because of the risk of hyperacute rejection mediated by preformed anti-ABO antibodies. The aim of the present study was to evaluate the outcome of liver transplants performed with ABO-incompatible living-donor livers and to detect risk factors for development of complications. From June 1990 to February 2000, 66 patients, 10 months to 55 years old (median, 2 years old), received 68 ABO-incompatible living-donor liver grafts. The antibody titer and clinical course were followed prospectively during a period ranging from 3 to 11 years. The 5-year patient survival was 59%, 76%, and 80% for ABO-incompatible, ABO-compatible, and ABO-identical grafts, respectively (P<0.01). In patients <1 year old, > or =1 to <8, > or =8 to <16, and and > or =16 years old, 5-year survival was 76%, 68%, 53%, and 22%, respectively. The incidence of intrahepatic biliary complications and hepatic necrosis in ABO-incompatible living-related grafts (18% and 8%, respectively) was significantly (P<0.0001) greater than in ABO-compatible and ABO-identical grafts (both 0.6% and 0%, respectively). Predictive risk factors for increased mortality and morbidity were age greater than 1 year and elevated anti-ABO titers before transplantation. ABO-incompatible liver transplantation was carried out with relative safety in infants <1 year old but was not satisfactory in children >1 year in long-term follow-up. Patients aged >8 years remain at considerable risk of early fatal outcome because of hepatic necrosis, and new strategies to prevent antibody-mediated rejection are required.

Study 3: outcome of ABO-incompatible kidney transplantation immunosuppression with tacrolimus, mycophenolate mofetil, and steroids

T o help decrease the shortage of donors, ABOincompatible living kidney transplantation is being performed. Because these patients have a higher risk of acute rejection, we have been using 1-week pretransplant immunosuppression with tacrolimus, mycophenolate mofetil, and methylprednisolone (TAC-MMF-MP), which has resulted in a marked reduction in acute humoral-vascular rejection without any serious complications. Forty-five patients with end-stage renal failure underwent ABO-incompatible living kidney transplantation at our institute between January 2000 and March 2003. There were 25 men and 19 women with a mean age of 33 years. Plasmapheresis was carried out to remove anti-AB antibodies before the kidney transplantation. In 2000, 13 patients were treated with TAC-MMF-MP without 1-week pretransplant immunosuppression (group 1). Since January 2001, we have been administering TAC (0.1 mg/kg/d)– MMF (1-2 g/d)–MP (125 mg/d) concomitantly with plasmapheresis starting from 1 week before transplantation. One week pretransplant immunosuppression with TAC-MMF-MP was given in 32 patients (group 2). In the induction phase, TACMMF-MP was used for posttransplant immunosuppression without any antibody administration, such as OKT-3 and antithymocyte globulin. Splenectomy was done at the time of kidney transplantation in all patients. Pretransplant anti-ABO antibody titer was 32 dilution or less in all cases. Patient survival was 100% in both treatment groups. Graft survival rates were 92% and 97 % in groups 1 and 2, respectively, which were almost the same as those of ABO-compatible patients. One patient in group 1 lost the graft because of severe pancreatitis, and 1 patient in group 2 lost the graft because of severe humoral rejection. The incidence rates of acute rejection were 56% (7/13) and 19% (6/32) in groups 1 and 2, respectively. Most episodes of acute rejection (about 80%) were vascular-humoral rejections in both groups. No patient experienced any severe infectious complication. Conclusion: Pretransplant immunosuppression for 1 week with TAC-MMF-MP in ABOincompatible living kidney transplantation offers an excellent outcome without any severe infectious complication. From the Department of Urology, Tokyo Women’s Medical University, Shinjuku, Tokyo, Japan. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.004

Long-term outcome of abo-incompatible renal transplantation

Based on the long-term experience with ABO-incompatible kidney transplantation, the following can be concluded: 1. Renal transplantation across ABO incompatibility is an acceptable treatment for patients with end-stage renal failure. [table: see text] 2. Long-term patient and graft survival in ABO-incompatible kidney transplantation is influenced primarily by acute rejection episodes occurring within 1 year. 3. Despite the removal of anti-ABO natural antibodies before transplantation, hyperacute rejection crises may occur in some cases. 4. Humoral rejection is the most prominent type of rejection in ABO-incompatible renal transplantation. Even though most of this rejection is controllable with anti-rejection therapy, the prognosis for a graft that undergoes humoral rejection is significantly poor. 5. The maximum IgG titers of anti-A/B antibody before transplantation may have a harmful effect on graft acceptance in ABO-incompatible kidney transplantation. 6. Renal transplantation across ABO incompatibility is principally the most significant risk factor to affect long-term allograft function in ABO-incompatible living kidney transplantation.

Comparative study of theefficacy of removal of anti-ABO and anti-gal antibodies by double filtration plasmapheresis.

Successful clinical ABO-incompatible renal transplantation has been achieved by the removal of anti-A or anti-B antibodies using double filtration plasmapheresis (DFPP). We have compared changes in the levels of anti-donor antibodies and the histopathology of the renal grafts following human ABO-incompatible allotransplantation and pig-to-baboon xenotransplantation using pretransplant DFPP. DFPP was performed on days 6, -4, -2 and -1 before the ABO-incompatible transplants (n=25) and on days -2 and 0 (immediately before reperfusion) in the xenotransplants (n=4). In two baboons (XenoTx Group I) the extent of antibody removal was comparable to that in the ABO-incompatible patients, and an even greater level of removal was achieved in another two baboons (XenoTx Group II). Anti-A and anti-B and anti-pig IgM and IgG antibodies were measured by flow cytometry. All clinical ABO-incompatible renal grafts are functioning, except two which were lost from recurrence of the original disease or from chronic rejection. Three other grafts underwent humoral rejection episodes, which were successfully treated. DFPP reduced the mean anti-A/B IgM and IgG antibody levels to 8% and 13% of pretreatment levels, respectively. After kidney transplantation, they were maintained at 37% and 46% of pre-DFPP level. No antibody binding to the transplanted kidney was detected at any time (1 h to 2 yr) after ABO-incompatible allotransplantation. In contrast, in XenoTx Group I, the same extent of antibody removal (90%) prevented hyperacute rejection, but the two grafts were rejected on days 6 and 7, respectively, from acute vascular rejection. In XenoTx Group II, the additional DFPP that was required to deplete the remaining 10% of anti-pig antibody was poorly tolerated and the two baboons died 4 h and 2 days, respectively, after renal transplantation. Although anti-pig IgM antibodies were reduced to 2% of pre-treatment level, IgM and C3 binding were detected in the graft as early as 1 h posttransplantation. These data suggest that the concentration of xeno-antigen epitopes expressed on pig organs may need to be reduced by genetic engineering to the much lower level of blood group A/B antigens on human kidneys if discordant xenotransplantation is to be successful.

Treatment of integrated traditional and western medicine in recurrent spontaneous abortion of immune abnormality type

Immune abnormality type of recurrent spontaneous abortion (RSA) is an important etiological type, major findings of that are the abnormal increases in auto and/or allo-antibodies of anti-zona pellucida, antiphospholipid and anti-ABO blood group. In the present study, to assess the clinical values of integrated traditional and Western medicine and its therapeutic mechanisms in treating immune abnormality type of RSA. Aborters were treated by Zhibai Dihuang Pills for anti-zona pellucida antibodies, and clear evil Heat, remove Dampness, replenish blood and activate circulation by Chinese medicinal herbs recipe for anti-phospholipid and anti-ABO group antibodies. After they had been treated by these recipe, 92.3% of them became pregnant with normal delivery. It was found in dynamic investigation that level of the antibodies turned to decrease gradually during the treatment, and that of anti-phospholipid and anti-ABO group antibodies increased again at beginning of pregnancy and then decreased gradually with continuing pregnancy. Chinese herbs recipe could be used to treat RSA of the immune abnormality type by way of decreasing the elevated levels of auto and/or allo-antibodies.

Donor-derived antibodies and hemolysis after ABO-compatible but nonidentical heart-lung and lung transplantation.

Organ donors and transplant recipients are routinely tested for ABO compatibility. ABO-identical organs are preferred, but occasionally the use of an ABO-compatible but nonidentical donor is clinically warranted. In heart-lung transplantation, the incidence of hemolysis from donor-derived anti-ABO antibodies is as high as 70%. The incidence of hemolysis for lung-only transplantation is not known. Our current posttransplantation transfusion policy for ABO-compatible but nonidentical lung-only transplant recipients is, when indicated, to use donor ABO group red blood cells. To evaluate the efficacy of our transfusion policy, we reviewed our experience from 1986-96. One heart-lung transplant, four single lung transplant, and three bilateral single lung transplant recipients received ABO-compatible but nonidentical organs. The heart-lung transplant recipient developed a positive direct antiglobulin test (DAT), with anti-A eluted, and severe hemolysis on postoperative day 8 requiring plasma and whole blood exchange. Four of six lung-only transplant patients tested developed a positive DAT with anti-A eluted. Two early lung-only patients, who did not receive donor ABO group red blood cells, demonstrated clinical and laboratory evidence of hemolysis. Three bilateral lung transplant recipients were followed prospectively. The first patient had a negative DAT. The next two patients developed positive DATs on postoperative day 8 and 10, respectively. No evidence of hemolysis was detected in any of these cases. These results confirm that donor-derived anti-ABO antibodies develop with lung-only transplants. Our current transfusion policy is justified for both heart-lung and lung recipients of ABO-compatible but nonidentical organs. A high index of suspicion for donor-derived antibody causing hemolysis and communication with blood bank personnel are mandatory in this setting.

Removal of anti-A/B antibodies for successful kidney transplantation between ABO blood type incompatible couples

A growing shortage of cadaveric donors has prompted expansion of the criteria for acceptable living donors. Because of this, ABO-incompatible kidney transplantation has been carried out. To remove anti-A and/or anti-B antibodies, the recipients received one or two sessions of double filtration plasmapheresis (DFPP) and three or four sessions of immunoadsorption prior to transplantation until the anti-A IgG/IgM titers and/or anti-B IgG/IgM titers decreased to 1: 16 or less. Our immunosuppressive protocol involved treatment with the drugs methylprednisolone, cyclosporine, azathioprine, anti lymphocyte globulin and deoxyspergualin. The patient survival was 98% at 1 month, 98% at 3 months, 94% at 6 months, and 92% at 1–5 years. Graft survival was 92% at 1 month, 88% at 3 months, 85% at 6 months, 81% at 1 year, and 76% at 5 years. Both DFPP and/or immunoadsorption eliminated anti-ABO antibodies from ABO-incompatible kidney transplant recipients effectively and safely. The results of the ABO-incompatible kidney transplantation were acceptable and not different from those of ABO-compatible cases.

Removal of anti-A/B antibodies for successful kidney transplantation between ABO blood type incompatible couples

A growing shortage of cadaveric donors has prompted expansion of the criteria for acceptable living donors. Because of this, ABO-incompatible kidney transplantation has been carried out. To remove anti-A and/or anti-B antibodies, the recipients received one or two sessions of double filtration plasmapheresis (DFPP) and three or four sessions of immunoadsorption prior to transplantation until the anti-A IgG/IgM titers and/or anti-B IgG/IgM titers decreased to 1: 16 or less. Our immunosuppressive protocol involved treatment with the drugs methylprednisolone, cyclosporine, azathioprine, anti lymphocyte globulin and deoxyspergualin. The patient survival was 98% at 1 month, 98% at 3 months, 94% at 6 months, and 92% at 1–5 years. Graft survival was 92% at 1 month, 88% at 3 months, 85% at 6 months, 81% at 1 year, and 76% at 5 years. Both DFPP and/or immunoadsorption eliminated anti-ABO antibodies from ABO-incompatible kidney transplant recipients effectively and safely. The results of the ABO-incompatible kidney transplantation were acceptable and not different from those of ABO-compatible cases.

Distribution of 486P 3/12 Antigen, Abo(H) Blood Group Antigen and T Antigen in Cystectomy Specimens from Patients with Stage T2 Transitional Cell Carcinoma of the Bladder

We used monoclonal antibody 486P 3/12, anti-ABO(H) antibodies and anti-T antigen lectins to detect malignant transformation in cystectomy specimens from patients with stage T2 transitional cell carcinoma of the bladder. We used an immunoperoxidase technique to do extensive chessboardlike mapping studies in 6 cystectomy bladders with stage T2 lesions and 1 normal bladder from a multiorgan donor as control to characterize antigen expression. Increased 486P 3/12 antigen expression, decreased ABO(H) expression and T antigen deletion were detectable not only in the tumor area but also in tumor-surrounding areas classified as benign. We believe that cells with abnormal antigen expression are a source of tumor recurrence and can be identified with our method of quantitative immunocytology.

Two induced anti-Z-DNA monoclonal antibodies use VH gene segments related to those of anti-DNA autoantibodies.

The cDNA for H and L chain V regions of two anti-Z-DNA mAb, Z22 and Z44, were cloned and sequenced. These are the first experimentally induced anti-nucleic acid antibody sequences available for comparison with autoantibody sequences. Z22 and Z44 are IgG2b and IgG2a antibodies from C57BL/6 mice. They recognize different facets of the Z-DNA structure. They both use VH10 family genes and share 95% sequence base sequence identity in the VH and leader sequences; however, they differ in the 5'-untranslated region of the VH mRNA, indicating they arise from different germline genes. Both use JH4 segments. They differ from each other very extensively in the CDR3 of both H and L chains. The most closely related H chains in the current GenBank/EMBL data base are two mouse IgG anti-DNA autoantibodies, one from an MRL-lpr/lpr mouse (MRL-DNA4) and one from an NZB/NZW mouse (BV04-01). Z22 and Z44 share 95% sequence identity with these antibodies in the VH segment. In addition, Z22 is identical to MRL-DNA4 at 91% of the positions in the 5'-untranslated region of the H chain mRNA. The two antibodies share 95% base sequence identity in the V kappa segment. The most closely related L chains, with 97 to 98% sequence identity, are the V kappa 10b germline gene for Z22 and the V kappa 10a germ line gene, which is associated with A/J anti-arsonate antibodies and BALB/c anti-ABO blood group substance antibodies, for Z44. Z22 and Z44 share several structural features (similarities in VH, JH, and V kappa) but differ very markedly in the L chain CDR1 and both H and L chain CDR3 sequences; these regions may determine the differences in their specific interactions with Z-DNA.

'AUTO’-Anti-ABO Antibodies after Organ Transplantation: a Ciclosporin A Related Phenomenon?

'AUTO’-Anti-ABO Antibodies after Organ Transplantation: a Ciclosporin A Related Phenomenon?

ABO-INCOMPATIBLE BONE-MARROW TRANSPLANTATION: REMOVAL OF RED BLOOD CELLS FROM DONOR MARROW AVOIDING RECIPIENT ANTIBODY DEPLETION

Eight patients with acute leukaemia undergoing allogeneic bone-marrow transplantation from ABO-incompatible donors received red-cell-depleted donor marrow without any procedure to diminish their anti-ABO antibody titres. Successful marrow red-cell removal (mean 98·8%) was achieved by means of a large- volume separation technique on Ficoll-Metrizoate in the IBM 2991 blood-cell processor. Clinically significant ABQ-haemolytic reaction was prevented in all patients, and there was neither failure of engraftment nor rejection. This approach used alone is satisfactory for most ABO-incompatible marrow-transplant recipients, although combining this with some method of recipient antibody depletion, such as plasma exchange, is recommended in the occasional patient with high anti-ABO titres.