Patient characteristics
| Patients evaluated for antibody levels against . | Polio . | Tetanus, H influenzae, and S pneumoniae . | ||||
|---|---|---|---|---|---|---|
| Source of stem cells . | Marrow, n = 40 . | PBSC, n = 47 . | Significance of difference* . | Marrow, n = 19 . | PBSC, n = 18 . | Significance of difference* . |
| Patient age at transplantation, y, median (range) | 43 (22-59) | 43 (18-61) | NS | 43 (22-59) | 43 (25-54) | NS |
| Donor age at transplantation, y, median (range) | 45 (24-65) | 40 (13-62) | NS | 40 (24-65) | 41 (13-62) | NS |
| Patient sex (%) | ||||||
| Males | 23 (58) | 30 (64) | NS | 10 (53) | 13 (72) | NS |
| Females | 17 (42) | 17 (36) | NS | 9 (47) | 5 (28) | NS |
| Donor-patient histocompatibility (%) | ||||||
| HLA-A, B, and DR-matched sibling | 40 (100) | 46 (98) | NS | 19 (100) | 17 (94) | NS |
| HLA-A, B, and DR-matched child | 0 (0) | 1 (2) | NS | 0 (0) | 1 (6) | NS |
| Disease/disease stage at transplantation†(%) | ||||||
| Good risk | 26 (65) | 26 (55) | NS | 9 (47) | 8 (44) | NS |
| Poor risk | 14 (35) | 21 (45) | NS | 10 (53) | 10 (56) | NS |
| First transplantation (%) | 40 (100) | 47 (100) | — | 19 (100) | 18 (100) | — |
| Cytomegalovirus (CMV) serostatus before transplantation (%) | ||||||
| Donor + and recipient + | 17 (43) | 13 (28) | NS | 7 (37) | 5 (28) | NS |
| Donor − and recipient + | 7 (18) | 11 (23) | NS | 3 (16) | 4 (22) | NS |
| Donor + and recipient − | 5 (13) | 11 (23) | NS | 3 (16) | 4 (22) | NS |
| Donor − and recipient − | 11 (28) | 11 (23) | NS | 6 (32) | 5 (28) | NS |
| Unknown or equivocal | 0 (0) | 1 (2) | NS | 0 (0) | 0 (0) | NS |
| Splenectomized patients (%) | 2 (5) | 1 (2) | NS | 0 (0) | 1 (6) | NS |
| Conditioning‡ (%) | ||||||
| Chemotherapy only | 24 (60) | 25 (53) | NS | 7 (37) | 9 (50) | NS |
| Chemotherapy plus TBI | 16 (40) | 22 (47) | NS | 12 (63) | 9 (50) | NS |
| GVHD prophylaxis with methotrexate and cyclosporine22(%) | 40 (100) | 47 (100) | — | 19 (100) | 18 (100) | — |
| Acute GVHD (%) | ||||||
| Grade 0-1 | 12 (30) | 15 (32) | NS | 5 (26) | 6 (33) | NS |
| Grade 2-41-153 | 28 (70) | 32 (68) | NS | 14 (74) | 12 (67) | NS |
| Chronic GVHD diagnosed by day 365 (%) | ||||||
| None or subclinical | 13 (33) | 6 (13) | NS1-164 | 6 (32) | 2 (11) | NS |
| Clinical limited | 8 (20) | 10 (21) | NS | 5 (26) | 4 (22) | NS |
| Clinical extensive1-155 | 19 (48) | 31 (66) | NS | 8 (42) | 12 (67) | NS |
| Chimerism status (%) | ||||||
| Full chimera1-154 | 39 (97) | 43 (87) | NS | 18 (95) | 17 (94) | NS |
| Unknown | 1 (3) | 4 (13) | NS | 1 (5) | 1 (6) | NS |
| Relapse between day 80 and 365# (%) | 2 (5) | 4 (9) | NS | 0 (0) | 1 (6) | NS |
| Death without relapse between day 80 and 365 (%) | 8 (20) | 3 (6) | NS | 3 (16) | 3 (17) | NS |
| Glucocorticoid treatment between day 50 and 365 (%) | 33 (83) | 38 (81) | NS | 16 (84) | 14 (78) | NS |
| IVIG administration between day 50 and 3651-160(%) | 2 (5) | 5 (11) | NS | 0 (0) | 1 (6) | NS |
| Patients evaluated for antibody levels against . | Polio . | Tetanus, H influenzae, and S pneumoniae . | ||||
|---|---|---|---|---|---|---|
| Source of stem cells . | Marrow, n = 40 . | PBSC, n = 47 . | Significance of difference* . | Marrow, n = 19 . | PBSC, n = 18 . | Significance of difference* . |
| Patient age at transplantation, y, median (range) | 43 (22-59) | 43 (18-61) | NS | 43 (22-59) | 43 (25-54) | NS |
| Donor age at transplantation, y, median (range) | 45 (24-65) | 40 (13-62) | NS | 40 (24-65) | 41 (13-62) | NS |
| Patient sex (%) | ||||||
| Males | 23 (58) | 30 (64) | NS | 10 (53) | 13 (72) | NS |
| Females | 17 (42) | 17 (36) | NS | 9 (47) | 5 (28) | NS |
| Donor-patient histocompatibility (%) | ||||||
| HLA-A, B, and DR-matched sibling | 40 (100) | 46 (98) | NS | 19 (100) | 17 (94) | NS |
| HLA-A, B, and DR-matched child | 0 (0) | 1 (2) | NS | 0 (0) | 1 (6) | NS |
| Disease/disease stage at transplantation†(%) | ||||||
| Good risk | 26 (65) | 26 (55) | NS | 9 (47) | 8 (44) | NS |
| Poor risk | 14 (35) | 21 (45) | NS | 10 (53) | 10 (56) | NS |
| First transplantation (%) | 40 (100) | 47 (100) | — | 19 (100) | 18 (100) | — |
| Cytomegalovirus (CMV) serostatus before transplantation (%) | ||||||
| Donor + and recipient + | 17 (43) | 13 (28) | NS | 7 (37) | 5 (28) | NS |
| Donor − and recipient + | 7 (18) | 11 (23) | NS | 3 (16) | 4 (22) | NS |
| Donor + and recipient − | 5 (13) | 11 (23) | NS | 3 (16) | 4 (22) | NS |
| Donor − and recipient − | 11 (28) | 11 (23) | NS | 6 (32) | 5 (28) | NS |
| Unknown or equivocal | 0 (0) | 1 (2) | NS | 0 (0) | 0 (0) | NS |
| Splenectomized patients (%) | 2 (5) | 1 (2) | NS | 0 (0) | 1 (6) | NS |
| Conditioning‡ (%) | ||||||
| Chemotherapy only | 24 (60) | 25 (53) | NS | 7 (37) | 9 (50) | NS |
| Chemotherapy plus TBI | 16 (40) | 22 (47) | NS | 12 (63) | 9 (50) | NS |
| GVHD prophylaxis with methotrexate and cyclosporine22(%) | 40 (100) | 47 (100) | — | 19 (100) | 18 (100) | — |
| Acute GVHD (%) | ||||||
| Grade 0-1 | 12 (30) | 15 (32) | NS | 5 (26) | 6 (33) | NS |
| Grade 2-41-153 | 28 (70) | 32 (68) | NS | 14 (74) | 12 (67) | NS |
| Chronic GVHD diagnosed by day 365 (%) | ||||||
| None or subclinical | 13 (33) | 6 (13) | NS1-164 | 6 (32) | 2 (11) | NS |
| Clinical limited | 8 (20) | 10 (21) | NS | 5 (26) | 4 (22) | NS |
| Clinical extensive1-155 | 19 (48) | 31 (66) | NS | 8 (42) | 12 (67) | NS |
| Chimerism status (%) | ||||||
| Full chimera1-154 | 39 (97) | 43 (87) | NS | 18 (95) | 17 (94) | NS |
| Unknown | 1 (3) | 4 (13) | NS | 1 (5) | 1 (6) | NS |
| Relapse between day 80 and 365# (%) | 2 (5) | 4 (9) | NS | 0 (0) | 1 (6) | NS |
| Death without relapse between day 80 and 365 (%) | 8 (20) | 3 (6) | NS | 3 (16) | 3 (17) | NS |
| Glucocorticoid treatment between day 50 and 365 (%) | 33 (83) | 38 (81) | NS | 16 (84) | 14 (78) | NS |
| IVIG administration between day 50 and 3651-160(%) | 2 (5) | 5 (11) | NS | 0 (0) | 1 (6) | NS |
— indicates not applicable.
Significance of difference between marrow and PBSC recipients. This was determined by Mann-Whitney-Wilcoxon signed rank test for patient and donor age. For all other characteristics, the significance was determined by χ2 test and, when appropriate, also by Fisher exact test. NS denotes not significant(P > .05, by both χ2 test and Fisher exact test when appropriate). The significance of differences between the marrow group evaluated for polio antibodies (n = 40) and the marrow subgroup evaluated for tetanus, H influenzae, and S pneumoniae antibodies (n = 19) and between the PBSC group evaluated for polio antibodies (n = 47) and the PBSC subgroup evaluated for tetanus,H influenzae, and S pneumoniaeantibodies (n = 18) was tested by the same statistical tests; for all the characteristics the differences were not significant (not shown in the table). More rigorous analyses, comparing the marrow subgroup evaluated for tetanus, H influenzae,and S pneumoniae (n = 19) with the marrow subgroup not evaluated for tetanus, H influenzae, andS pneumoniae (n = 21) disclosed a near-significant difference in the proportion of patients with good-risk disease/disease stage (P = .06 by χ2 test and P = .05 by Fisher exact test) and a significant difference in the proportion of patients conditioned with TBI (P = .01 by χ2 test and P = .01 by Fisher exact test). The comparison of the PBSC subgroup evaluated for tetanus, H influenzae, and S pneumoniae (n =18) with the PBSC subgroup not evaluated for tetanus, H influenzae, andS pneumoniae (n = 29) disclosed a significant difference in the proportion of patients dying without relapse between days 80 and 365 (P = .04 by χ2test and P = .03 by Fisher exact test).
Good risk: chronic myelogenous leukemia in first chronic or accelerated phase, acute leukemia in first remission, refractory anemia, and myelofibrosis. Poor risk: chronic myelogenous leukemia in blast crisis, acute leukemia beyond first remission, refractory anemia with excess blasts, lymphoma, and multiple myeloma.
All conditioning regimens were myeloablative. The most frequent chemotherapy only regimen was IV cyclophosphamide (120 mg/kg) with PO busulfan (approximately 16 mg/kg). The most frequent chemotherapy plus TBI regimen was cyclophosphamide (120 mg/kg) with fractionated TBI (12.0-13.2 Gy). Four patients from the “chemotherapy plus TBI” group received fractionated total marrow irradiation (9.0 Gy, similar to upper mantle and inverted Y) instead of TBI (1 marrow recipient and 3 PBSC recipients).
Typically treated with prednisone 1-2 mg/kg/d PO for 10 to 14 days with subsequent taper over 50 days.
Typically treated with prednisone (0.5-1.0 mg/kg every other day PO) plus cyclosporine (approximately 6 mg/kg every other day PO) for at least 9 months.
At least 90% marrow cells of donor origin by day 80.
#For chronic myelogenous leukemia, the detection of bcr/abl transcript by PCR in the absence of cytogenetic or hematologic relapse was not considered a relapse. Because the goal of the study was to evaluate transplantation-associated immune deficiency and not malignancy-associated immune deficiency, antibody levels of patients who relapsed after transplantation were evaluated only before the diagnosis of relapse.
Intravenous immunoglobulin (IVIG), typically 200 mg/kg weekly before day 100, and 500 mg/kg monthly after day 100 until preinfusion level of 400 mg/dL has been achieved. Antibody levels in sera obtained within 2 months after the administration of intravenous immunoglobulin were not evaluated.
Significant by χ2 test for linear trend with 1 degree of freedom (P = .03). Similarly, if the groups with limited and extensive clinical chronic GVHD are collapsed into a group of any clinical chronic GVHD, then the percent PBSC recipients with any clinical chronic GVHD may be higher than the percent marrow recipients with any clinical chronic GVHD (P = .05, χ2 test; P = .04, Fisher exact test).