Biology of Blood and Marrow Transplantation
Volume 15, Issue 10 , Pages 1258-1264, October 2009

Partially Matched Related Hematopoietic Stem Cell Transplantation without Ex Vivo T Cell Depletion Compared with Matched Unrelated Transplantation in Adult Patients with Hematologic Malignancies

Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China

Received 27 March 2009; accepted 28 May 2009. published online 27 July 2009.

Article Outline

The optimal alternative donor for adult hematopoietic stem cell transplantation (HSCT) candidates who lack an ideal histocompatible sibling remains controversial. We studied the clinical outcomes of 88 adult patients with hematologic malignancies who received a partially matched related donor (PMRD) transplant (n=36) or a matched unrelated donor (MUD) transplant (n=52) with a uniform myeloablative protocol without ex vivo T cell depletion. Age and other characteristics were comparable in the 2 groups, except that the PMRD group had a higher proportion of bone marrow (BM) grafts. Primary engraftment was achieved in nearly 98% of the whole cohort. The incidences of acute grade III-IV and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 15% and 16% in the PMRD group and 16% and 14% in the MUD group. Although treatment-related mortality (TRM) was 42% in the PMRD group and 31% in the MUD group (P=.29), the relapse rate was<11% for the whole cohort. With a median follow-up of 30 months, no statistically significant difference was observed in 3-year overall survival (OS) and event-free survival (EFS) between the PMRD group (45% and 38%) and the MUD group (54% and 50%). These data demonstrate that HSCT performed with PMRD can be an alternative option for treating adult patients with hematologic malignancies.

Key Words: Partially matched related, Unrelated, Hematopoietic stem cell transplantation, Hematologic malignancy

 

Back to Article Outline

Introduction 

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially life-saving treatment for many hematologic malignancies. But, for patients lacking an ideal histocompatible sibling, the choice of the best alternative donor remains a matter of debate, because of the lack of data on outcomes from randomized controlled trials involving matched unrelated donor (MUD), umbilical cord blood (UCB), and partially matched related donor (PMRD) transplants 1, 2, 3, 4, 5.

For adults, transplantation using UCB has not yet been widely accepted because of concerns about the low number of stem cells present in graft collections, although transplantation of 2 units shows promise 6, 7. PMRD transplants have several advantages over MUD transplants, including immediate availability for virtually all patients (particularly important for those requiring urgent transplantation), significant cost savings, the ability to select the best donor among all relatives, optimal graft composition, and the availability of donor lymphocyte infusion (DLI) after transplantation if necessary [8].

Work on PMRD transplants has been ongoing for more than 20 years. Early experiences indicated inferior overall survival (OS) associated with transplantation of PMRD grafts compared with MUD grafts 9, 10. A study of 129 patients who received a MUD or PMRD transplant found a significantly better 2-year OS in the MUD group (58% vs 21%; P=.002) [10]. Since that time, however, significant improvements in conditioning regimens and graft manipulations have resulted in substantially improved outcomes for PMRD HSCT [8]. Impressive survival rates of around 50% have been reported in 2 large-scale reports, and conflicting data against the inferior outcome of PMRD transplant also have surfaced 5, 11, 12, 13. Making a conclusive decision regarding transplant type remains difficult, because of the heterogeneity of the patient populations and regimens used in different studies. Controversy about the relative merits of PMRD versus MUD persists, and further research is warranted.

In this study, we retrospectively analyzed data on adult patients who underwent HSCT in our center between 2003 and 2008 with either a PMRD or MUD transplant after myeloablative (MA) conditioning, to assess the impact of donor source on clinical outcomes.

Back to Article Outline

Patients and Methods 

Patients 

A total of 88 consecutive patients aged>18 years who underwent PMRD (n =36) or MUD (n=52) HSCT for a hematologic malignancy with a uniform protocol in our Hematology Department between July 2003 and June 2008 were enrolled in this study. All patients and donors provided written informed consent for the protocol, which was approved by our hospital's Ethics Committee. Patient characteristics are summarized in Table 1. Patients in complete remission (CR) with high risk included those with acute leukemia with unfavorable cytogenetic data at diagnosis, secondary leukemia, in second or further remission, and chronic myelogenous leukemia (CML) not in the first chronic phase (CP). Patients with other diseases were considered to be at standard risk. More information on the donor–recipient relationships and HLA disparities in the PMRD group is provided in Table 2.

Table 1. Characteristics of patients and grafts
CharacteristicPMRD GraftsMUD GraftsP
Recipients, n3652
Median age, years (range)24 (18-47)26 (18-49).516
Sex, male/female21/1539/13.099
Diagnosis .281
Acute myelogenous leukemia815
Acute lymphocytic leukemia1322
Chronic myelogenous leukemia1114
Non-Hodgkin lymphoma41
Disease status .186
CR with low risk1423
CR with high risk1828
Refractory/relapsed41
Graft type <.001
PBSCs alone045
BM alone237
BM+PBSCs130
Cell dose
CD34+×106/kg5.7 (3.4-9.3)4.9 (2.4-18.3).714
CD3+×107/kg9.6 (2.9-36.7)29.6 (10.7-62.3)<.001

PMRD indicates partially matched related donor; MUD, matched unrelated donor; CR, complete remission; PBSCs, peripheral blood stem cells; BM, bone marrow.

Table 2. Characteristics of PMRD graft recipients
CharacteristicQuantity
Recipients, n36
Donor/recipient relationship
Mother/child23 (63.9%)
Father/child1 (2.8%)
Child/mother2 (5.6%)
Child/father4 (11.1%)
Siblings6 (16.7%)
HLA disparity in the graft-versus-host direction at HLA-A, -B, and -DR
11 (2.8%)
216 (44.4%)
319 (52.8%)

PMRD indicates partially matched related donor.

HLA Typing 

HLA-A, -B, -C, and -DRB1 typing of the recipients and unrelated donors were performed by high-resolution DNA typing techniques using polymerase chain reaction (PCR) with sequence-specific primers. PMRD grafts were typed at low resolution for HLA-A, -B and –DR. For comparison of HLA matching between partially matched related pairs, the high-resolution HLA data of the recipients were converted to low-resolution equivalents.

Conditioning 

Patients with myelogenous leukemia received a conditioning regimen consisting of cytarabine 4g/m2/day (on days −10 and −9), busulfan (Bu) 3.2mg/m2/day i.v. (on days −8 to −6), cyclophosphamide (Cy) 1.8g/m2/day (on days −5 to −4), semustine 250mg/m2/day (on day −3), and rabbit antithymocyte globulin (ATG; Genzyme, Cambridge, MA) 2.5mg/kg/day (on days −5 to −2). Patients with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) received a similar regimen, but with total body irradiation (TBI; 8Gy, lung shielding at 6.5Gy, on day -6) substituted for Bu and cytarabine started on day -8.

Graft-versus-Host Disease Prophylaxis 

Graft-versus-host disease (GVHD) prophylaxis consisted of continuous cyclosporine (CsA) infusion at 3mg/kg/day starting on day -10, mycophenolate mofetil (MMF) 1.0g/day from days -10 to +30, and short-term methotrexate (MTX) given on days +1, +3, +6, and +11 at doses of 15, 10, 10, and 10mg/m2, respectively.

The onset and grades of acute and chronic GVHD (aGVHD, cGVHD) were assessed according to published consensus criteria 14, 15. The first-line treatment for aGVHD was based on the administration of methylprednisolone 2mg/kg/day in the event that grade≥II aGVHD developed.

Hematopoietic Stem Cell Collection and Supportive Care 

Donors were primed with granulocyte colony-stimulating factor (G-CSF) injected s.c. at a dose of 300μg/day for 5 consecutive days before stem cell harvesting. PMRD recipients received bone marrow (BM) or BM plus peripheral blood stem cells (PBSCs) if the number of CD34+ cells in the BM harvest was<3.0×106 cells/kg. No extra manipulation was produced to the inoculum before infusion, except to remove red cells and plasma in cases of ABO incompatibility.

All patients received cytomegalovirus (CMV) prophylaxis with ganciclovir for 10 days before transplantation and an s.c. injection of G-CSF 300μg starting on day 7 until the absolute neutrophil counts (ANCs) were>0.5×109/L. Standard prophylactic antibiotics were administered in accordance with institutional guidelines.

DLI 

Patients with relapse, persistent minimal residual disease, or decreased donor chimerism with no response to immunosuppressive drug alteration were candidates for DLI therapy. Cells were from cryopreserved PBSCs for unrelated recipients. PMRD recipients received newly G-CSF–mobilized PBSCs.

Endpoints and Definitions 

Outcome was documented in terms of engraftment, GVHD, treatment-related mortality (TRM), relapse, OS, and event-free survival (EFS). Time to engraftment was assessed according to standard criteria, with donor cell engraftment determined on marrow samples of recipients using quantitative PCR of informative short tandem repeat regions. Graft failure was defined as failure to achieve and maintain a neutrophil count>0.5×109/L. TRM was defined as death in continuous CR; OS, as the time interval from the date of transplantation to the date of death; and EFS, as the time from transplantation to treatment failure (death or relapse).

Statistical Analysis 

Comparisons of patient characteristics were performed using the χ2 or Fisher's exact test for categorical variables and the Mann-Whitney test for continuous variables. Cumulative incidence curves were used to calculate the probability of aGVHD, using TRM and relapse as competing risks. The probability of OS and EFS were estimated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors for OS and EFS (all baseline variables listed in Table 1) were examined in the Cox proportional hazards model. All statistical analyses conducted were based on data available on January 31, 2009, and performed with SPSS version 11.0. All P values are 2-sided. Results were considered statistically significant when P < .05.

Back to Article Outline

Results 

Engraftment 

Of the 88 patients in the cohort, 87 were evaluable for engraftment; 1 MUD recipient died 2 days after HSCT of sepsis-associated multiple-organ failure. Two patients in the PMRD group, 1 with refractory acute myelogenous leukemia (AML) and 1 with relapsed ALL at transplantation, demonstrated disease progression before achieving this endpoint. All other patients achieved neutrophil engraftment. The percentage of patients achieving engraftment did not differ significantly between the 2 groups (P = .17). The median time to neutrophil recovery was 12 days (range, 10 to 20 days) in the PMRD group and 13 days (range, 11 to 19 days) in the MUD group. The median time to recovery of platelet counts of>20×109/L was 19 days (range, 13 to 42 days). Three patients in PMRD group who died before achieving full platelet engraftment were excluded from the analysis. There was no statistically significant difference in the speed of platelet engraftment between the 2 groups. One patient in PMRD group experienced later graft failure on day 45, but subsequently achieved durable engraftment after receiving DLI. Analysis of DNA polymorphism confirmed complete donor chimerism of all of the patients after hematopoietic recovery.

Back to Article Outline

GVHD 

As shown in Figure 1, of the 85 patients evaluable for GVHD, the cumulative incidence of grade II-IV aGVHD at 100 days in patients who received PMRD grafts was 41% (95% confidence interval [CI], 25% to 58%), and 33% for those who received MUD grafts (95% CI, 20% to 46%) (P = .34). The incidence of grade III-IV aGVHD was 15% in the PMRD group and 16% in the MUD group. The proportion of patients with steroid-refractory aGHVD was 39% for the whole cohort.

In 69 patients (25 PMRD, 44 MUD) surviving and in remission beyond day 100, the cumulative risk of developing cGVHD was 48% (95% CI, 28% to 68%) in the PMRD group and 32% (95% CI, 18% to 46%) in the MUD group (P = .18). Although the rate of cGVHD was slightly higher in the PMRD group than in the MUD group, the incidence of extensive cGVHD was almost equivalent in the 2 groups (16% vs 14%, P = .99).

TRM and Relapse 

A total of 31 patients died because of TRM, which included infections (n=18), GVHD (n=11), and other toxicities (n=2), resulting in a rate of 42% (95% CI, 26% to 58%) in the PMRD group and 31% (95% CI, 18% to 44%) in the MUD group. Infection contributed to the majority of deaths in the whole cohort (18 of 31 deaths; 58%), but nearly all of these patients had ongoing GVHD or were receiving immunosuppressive therapy for GVHD prevention.

Nine patients (4 in the PMRD group and 5 in the MUD group) had relapsed by the time of the last follow-up. Of note, all 4 of the patients in the PMRD group received DLI; of these, 2 patients achieved CR, 1 patient is still alive in CR for 6 months, and 1 patient died of a second relapse 2 years later.

Survival 

The median follow-up time for the whole cohort was 30 months (range, 6 to 67 months). That for the PMRD group was 42 months (range, 6 to 67 months), and that for the MUD group was 27 months (range, 6 to 66 months). Overall, 39 patients died. The estimated probability of OS at 3 years after HSCT was 50% for the whole cohort (45% for the PMRD group vs 54% for the MUD group; P=.11). Likewise, the 3-year probability of EFS did not differ significantly between the 2 groups (38% for the PMRD group vs 50% for the MUD group; P=.12) (Figure 2). These results were confirmed in a multivariate regression model (Table 3). Because mothers accounted for the majority of the donors in the PMRD group, we also calculated the survival rate of this cohort. Notably, although 13 of these patients (57%) belonged to the high-risk group, the 3-years OS was 52% and the 3-year EFS was 49%, similar to the rates for the MUD group.

Table 3. Multivariate analysis of factors associated with OS and EFS
OSEFS
ParameterHazard ratio (95% CI)PHazard ratio (95% CI)P
Age
≤ median1.111.37
> median1.04 (0.99-1.09) 1.02 (0.98-1.07)
Donor–recipient sex pair
Female-to-male1.391.30
Other combinations0.75 (0.39-1.44) 0.71 (0.37-1.35)
Disease status
Low1.041.07
High2.05 (1.02-4.14) 1.85 (0.95-3.63)
Graft type
BM only1.821.92
With PBSCs0.91 (0.40-2.07) 1.05 (0.46-2.36)
Donor type
PMRD1.081.18
MUD0.25 (0.05-1.17) 0.36 (0.08-1.61)

OS indicates overall survival; EFS, event-free survival; BM, bone marrow; PBSCs, peripheral blood stem cells; PMRD, partially matched related donor; MUD, matched unrelated donor.

Back to Article Outline

Discussion 

This retrospective single-center study comparatively analyzed transplantation outcomes in a consecutive series of adult patients who underwent myeloablative (MA) allogeneic HSCT in a uniform fashion from either matched unrelated or HLA-disparate family donors. Our data confirm that the outcomes of HSCT performed with PMRD grafts are comparable to those of HSCT performed with MUD grafts.

Both T cell–replete and T cell–depleted (TCD) strategies have been evaluated in an effort to overcome the complications after mismatched related HSCT [16]. Unmanipulated graft transplantation has at least 2 advantages over the in vitro TCD approach: (1) easier to perform and less expensive, and (2) more rapid donor T cell recovery, which is crucial to provide a tangible graft-versus-leukemia effect for patients with advanced malignancies 12, 17. Distinct from early clinical experience with T cell–replete HSCT with a significant incidence of GVHD [18], the incidence of serious a GVHD was kept<20% with proper pharmacologic prophylaxis in our study, in agreement with incidences reported by other authors 5, 11.

The rates of serious aGVHD and extensive cGVHD were very similar in the 2 groups (15% and 16% in PMRD group vs 16% and 14% in MUD group), although the rates of severe aGVHD and cGVHD were slightly higher in the PMRD group. We believe that the fact that more patients in the PMRD group received G-CSF–primed BM grafts may have contributed to a protective effect. Previous studies have found that G-CSF priming significantly increased the number of CD34+ cells, reduced the number of total lymphocytes, and reversed the CD4+:CD8+ ratio in the donor marrow 19, 20. Thus, G-CSF–primed BM may offer some or all of the benefits of PBSCs, whereas avoiding the risks of PBSCs. Given the pain associated with BM harvest and the risk of anesthesia in the procedure, this characteristic is an inherent advantage of PMRD grafts, as is the feasibility of obtaining additional donor cells for immunotherapy after transplantation. Nevertheless, this advantage of primed BM failed to improve patient outcomes in multivariate analysis (Table 3), indicating that stem cell source actually may not be a prognostic factor for survival 11, 21.

The other potential explanation for the low incidence of serious GVHD in the PMRD group is the administration of a combination of ATG and other immunosuppressive agents. This combination provides sufficient immunosuppression to offset the disadvantage of HLA disparity. Recent findings have demonstrated that ATG, a polyclonal antibody targeting a broad range of T cells, has diverse immunomodulatory activities beyond T cell depletion, suggesting a positive role in immune recovery after transplantation [22]. Furthermore, relapse rates as low as 11% in our study and other studies indicate that ATG does not influence the antitumor effect 11, 13. Lu et al. [11] reported an estimated risk of relapse at 2 years of 14% in patients receiving a PMRD graft, compared with 13% in those receiving a matched sibling graft without ATG administration. Beyond ATG, some novel potent immunosuppressive agents, such as alemtuzumab and sirolimus, are now available [23], and preliminary data suggest exciting results in this context 24, 25.

In our study, the 3-year EFS for the PMRD group of 38% is slightly worse than that reported by the Beijing group of Lu et al. [11] using an almost-identical regimen. In addition to the heterogeneity of the patient age and disease composition, we also note that the Beijing group used grafts with a small BM harvest (median CD34+ cell dose, 2.3×106/kg). Megadose CD34+ cells are known to have veto activity in the TCD setting, which might affect transplant outcomes [26]. Whether or not this factor might contribute to the discrepancy between the 2 centers in non-TCD matters awaits further study.

It should be noted that even though the difference in long-term survival did not reach statistical significance between our 2 groups, a slight trend toward higher mortality mainly resulting from TRM after PMRD transplantation was found to exist. Fortunately, several measures to counteract the disadvantage of HLA mismatching may be available in the near future.

In our practice, if a patient is eligible for allogeneic HSCT, but has no matched related donor, then we generally wait for the results of an MUD search first, rather than considering PMRD transplantation immediately. In fact, the time from diagnosis to transplantation has been shown to be a negative prognostic factor [3]. Thus, to decrease the accumulation of chemotherapy-induced toxicity and likelihood of disease progression, it might be appropriate to consider PMRD HSCT as an initial treatment in patients requiring urgent transplantation.

Another important way to decrease TRM is to use reduced-intensity conditioning (RIC). After its extraordinary success in MUD HSCT, RIC is currently being explored as an option in PMRD transplantation in selected patients [27]. In one of the largest series to date, 49 adult patients who received an unmanipulated PBSC transplant after RIC consisting of alemtuzumab, fludarabine (Flu), and Cy had a TRM rate of only 10.2% and a 1-year OS for standard-risk patients of 63% [17]. Burroughs et al. [5] reported the outcomes of 28 patients with refractory or relapsed Hodgkin lymphoma (HL) who received a haploidentical transplant using a different conditioning regimen. Compared with HLA-matched related recipients, the haploidentical transplant recipients had a significantly lower TRM (hazard ratio, 0.14; 95% CI, 0.0 to 0.7; P=.02) and better 2-year progression-free survival (PFS). For high-risk patients, conclusions based on these results should still be viewed with caution, however.

In the present study, we found that patients receiving a mother donor transplant had a relatively better outcome, with a 3-year OS of 52%. Although our low patient numbers does not allow us to draw any firm conclusions, these data may support the hypothesis that a better survival can be expected in patients receiving maternal grafts. It has been proposed that, in both T cell–replete and TCD circumstances, patients receiving a maternal graft had better survival than those receiving a paternal graft 28, 29. This discrepancy is speculated to be the result of a confrontation between the immune systems of mother and offspring during pregnancy, leading to immunologic hyporesponsiveness (decreased GVHD hazard) or immunologic sensitization (enhanced graft-versus-leukemia effect) 28, 29. Contradictory results also have been reported, however 11, 30. In fact, many other donor factors (e.g.,degree of HLA incompatibility, natural killer cell alloreactivity, age, female donor for male patients, CMV status) have been associated with outcome in separate studies, but have not been addressed in a comprehensive fashion 3, 4, 31, 32. A large-scale study to generate an applicable scoring system based on these variables can help determine the most appropriate donor selection.

In conclusion, within the limitation of a retrospective study, we have demonstrated that HSCT with PMRD grafts without ex vivo TCD may not compromise outcome compared with HSCT with MUD grafts. In light of continuous improvements in transplantation technology, performing PMRD HSCT in a subset of patients lacking a HLA-matched sibling donor is an acceptable choice.

Back to Article Outline

Acknowledgments 

Financial disclosure: This study was supported by the grant of the Medical Academic Leader Foundation Program of Jiangsu Province (2007106). The authors thank all of the physicians, nurses, and support personnel for their dedicated care of patients in this study.

Back to Article Outline

References 

  1. Hwang WY, Samuel M, Tan D, et al. A meta-analysis of unrelated donor umbilical cord blood transplantation versus unrelated donor bone marrow transplantation in adult and pediatric patients. Biol Blood Marrow Transplant. 2007;13:444–453
  2. Atsuta Y, Suzuki R, Nagamura-Inoue T, et al. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. Blood. 2009;113:1631–1638
  3. Ottinger HD, Ferencik S, Beelen DW, et al. Hematopoietic stem cell transplantation: contrasting the outcome of transplantations from HLA-identical siblings, partially HLA-mismatched related donors, and HLA-matched unrelated donors. Blood. 2003;102:1131–1137
  4. Caillat-Zucman S, Le Deist F, Haddad E, et al. Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-center comparative analysis of genoidentical, haploidentical or unrelated donors. Bone Marrow Transplant. 2004;33:1089–1095
  5. Burroughs LM, O'Donnell PV, Sandmaier BM, et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14:1279–1287
  6. Tse W, Bunting KD, Laughlin MJ. New insights into cord blood stem cell transplantation. Curr Opin Hematol. 2008;15:279–284
  7. Majhail NS, Brunstein CG, Wagner JE. Double umbilical cord blood transplantation. Curr Opin Immunol. 2006;18:571–575
  8. Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008;41:473–481
  9. Szydlo R, Goldman JM, Klein JP, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15:1767–1777
  10. Drobyski WR, Klein J, Flomenberg N, et al. Superior survival associated with transplantation of matched unrelated versus one-antigen–mismatched unrelated or highly human leukocyte antigen–disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts. Blood. 2002;99:806–814
  11. Lu DP, Dong L, Wu T, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood. 2006;107:3065–3073
  12. Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–3454
  13. Chen XH, Zhang C, Zhang X, et al. Role of antithymocyte globulin and granulocyte-colony stimulating factor–mobilized bone marrow in allogeneic transplantation for patients with hematologic malignancies. Biol Blood Marrow Transplant. 2009;15:266–273
  14. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–828
  15. Atkinson K, Horowitz MM, Gale RP, et al. Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International. Bone Marrow Transplant Registry. Bone Marrow Transplant. 1989;4:247–254
  16. Kang Y, Chao NJ, Aversa F. Unmanipulated or CD34 selected haplotype mismatched transplants. Curr Opin Hematol. 2008;15:561–567
  17. Rizzieri DA, Koh LP, Long GD, et al. Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol. 2007;25:690–697
  18. Beatty PG, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med. 1985;313:765–771
  19. Ji SQ, Chen HR, Wang HX, et al. G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia. Bone Marrow Transplant. 2002;30:861–866
  20. Frangoul H, Nemecek ER, Billheimer D, et al. prospective study of G-CSF–primed bone marrow as a stem cell source for allogeneic bone marrow transplantation in children: a Pediatric Blood and Marrow Transplant Consortium (PBMTC) study. Blood. 2007;110:4584–4587
  21. Morton J, Hutchins C, Durrant S. Granulocyte colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF–mobilized peripheral blood stem cells. Blood. 2001;98:3186–3191
  22. Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21:1387–1394
  23. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351:2715–2729
  24. von Reyn Cream L, Ehmann WC, Rybka WB, et al. Sirolimus in unmanipulated haploidentical cell transplantation. Bone Marrow Transplant. 2008;42:765–766
  25. Kanda Y, Oshima K, Asano-Mori Y, et al. In vivo alemtuzumab enables haploidentical human leukocyte antigen–mismatched hematopoietic stem cell transplantation without ex vivo graft manipulation. Transplantation. 2005;79:1351–1357
  26. Gur H, Krauthgamer R, Berrebi A, et al. Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34(+) cells. Blood. 2002;99:4174–4181
  27. Dey BR, Spitzer TR. Current status of haploidentical stem cell transplantation. Br J Haematol. 2006;135:423–437
  28. Tamaki S, Ichinohe T, Matsuo K, et al. Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts. Bone Marrow Transplant. 2001;28:375–380
  29. Stern M, Ruggeri L, Mancusi A, et al. Survival after T cell–depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood. 2008;112:2990–2995
  30. van Rood JJ, Loberiza FR, Zhang MJ, et al. Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood. 2002;99:1572–1577
  31. Ciceri F, Labopin M, Aversa F, et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood. 2008;112:3574–3581
  32. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–2100

 Financial disclosure: See Acknowledgments on page 1263.

PII: S1083-8791(09)00272-9

doi:10.1016/j.bbmt.2009.05.020

Biology of Blood and Marrow Transplantation
Volume 15, Issue 10 , Pages 1258-1264, October 2009

Article Tools

* Image Usage & Resolution