CBF

i. Cord Blood Transplants

  1. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Blood. 2009 113:2902-5.

Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in complete remission [CR]) received reduced intensity conditioning (RIC) followed by allogeneic transplantation. All patients were high risk. After a uniform preparative regimen (fludarabine 40 mg/m2 x 5, cyclophosphamide 50 mg/kg, 200 cGy total body irradiation), patients received either matched related (n = 4) or umbilical cord (n = 18) donor grafts. All patients reached neutrophil engraftment and 100% donor chimerism (median, days 10 and 23, respectively). Overall survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3 years, respectively. There were no relapses beyond 2 years. The cumulative incidence of acute and chronic graft-versus-host disease was 55% and 45%. Hematopoietic cell transplantation in CR1 (n = 14) led to significantly less TRM (8%, P < .04) and improved overall survival (81%, P <.01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival.

The authors comment that survival can be improved using RIC HCT, RIC allograft for adult ALLA may limit TRM, particularly if performed in CR1. Rapid, complete donor engraftment was achieved without donor lymphocyte infusion. The data indicate that overall survival for ALL patients following RIC HCT is comparable to that achieved with conventional allografting. The authors suggest that UCB is a valuable option for older patients with ALL who lack a matched or sufficiently healthy sibling donor. The otherwise dismal prognosis of advanced ALL in adults suggests that the prevention of relapse with allografting in CR1 is the best opportunity to achieve long-term survival.

  1. Umbilical cord blood transplantation after reduced-intensity conditioning for elderly patients with hematologic diseases. Uchida N, Wake A, Takagi S, Yamamoto H, Kato D, Matsuhashi Y, Matsumura T, Seo S, Matsuno N, Masuoka K, Kusumi E, Yuji K, Miyakoshi S, Matsuzaki M, Yoneyama A, Taniguchi S. Biol Blood Marrow Transplant. 2008;14:583-590.

UCBT with reduced-intensity pretransplant conditioning (RI-UCBT) for adults, mostly younger than 55 years old, has been increasingly reported. However, less information is available regarding RI-UCBT in elderly patients.

The authors analyzed patients aged 55 years and older with hematologic diseases who underwent RI-UCBT. Patients were eligible for the study if they had any hematologic malignancy at high risk for relapse or severe aplastic anemia.

The authors commented on several observations that they made: First and foremost, RI-UCBT was a feasible treatment strategy for elderly patients with a successful engraftment rate of 92% without secondary graft failure except disease progression.

The average interval between transplant and neutrophil recovery to 500/µL was 18 days. A significant number of patients died from treatment-related complications, particularly from infections although the time to engraftment in this series was not delayed. Chimerism studies confirmed rapid engraftment of donor cells in all engrafted patients. The authors stated that their pretransplant conditioning regimens, mainly consisting of Flu, Mel, and TBI, along with single calcineurin inhibitors for GVHD prophylaxis can exert sufficient immunosuppressive effects that allow engraftment of CB cells.

Both the overall survival (OS) and progression-free survival (PFS) were estimated as 23% at 2 years posttransplant. This is slightly less than data reported previously, which can be reasonably explained by higher age range and poor disease status before transplant in this study cohort and which is further supported by the result of subgroup analysis indicating those with standard disease status showed mulch better outcome.

The authors stated that this is the first study specifically focusing on elderly patients aged 55 years and older with advanced hematologic disease to show the feasibility of RI-UCBT. Older age per se cannot be considered to be a contraindication to RI-UCBT.

  1. Reduced-intensity allogeneic transplant in patients older than 55 years: unrelated umbilical cord blood is safe and effective for patients without a matched related donor. Majhail NS, Brunstein CG, Tomblyn M, Thomas AJ, Miller JS, Arora M, Kaufman DS, Burns LJ, Slungaard A, McGlave PB, Wagner JE, Weisdorf DJ. Biol Blood Marrow Transplant. 2008;14:282-9.

The authors hypothesized that reduced-intensity conditioning (RIC) hematopoietic cell transplants (HCT) using UCB would be safe and efficacious in older patients. They compared the treatment-related mortality (TRM) and overall survival (OS) of RIC HCT in patients older than 55 years using either an adult matched related donor (MRD) (n = 47) or, in patients with no 5 of 6 or 6 of 6 HLA compatible related donors, UCB (n = 43).

The RIC regimen consisted of total-body irradiation (TBI; 200 cGy) and either cyclophosphamide and fludarabine (n = 69), or busulfan and fludarabine (n = 16) or busulfan and cladribine (n = 5). The median age of MRD and UCB cohorts was 58 (range, 55-70) and 59 (range, 55-69) years, respectively. Acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) (50%) was the most common diagnosis. All MRD grafts were 6 of 6 HLA matched to the recipient. Among patients undergoing UCB HCT, 88% received 2 UCB units to optimize cell dose and 93% received 1-2 HLA mismatched grafts. The median follow-up for survivors was 27 (range: 12-61) months.

The 3-year probabilities of progression-free survival (PFS; 30% versus 34%, P = .98) and OS (43% versus 34%, P = .57) were similar for recipients of MRD and UCB. The cumulative incidence of grade II-IV acute graft-versus-host (aGVHD) disease (42% versus 49%, P = .20) and TRM at 180-days (23% versus 28%, P = .36) were comparable. However, UCB recipients had a lower incidence of chronic graft-versus-host disease (cGVHD) at 1 year (40% versus 17%, P = .02). On multivariate analysis, graft type had no impact on TRM or survival, and the HCT comorbidity index score was the only factor independently predictive for these endpoints.

The investigators conclude that their study supports the use of HLA mismatched UCB as an alternative graft source for older patients who need a transplant but do not have an MRD. The use of RIC and UCB extends the availability of transplant therapy to older patients previously excluded on the basis of age and lack of a suitable MRD. A careful review of existing comorbidities is necessary when considering older patients for HCT.

  1. Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases. Bradley MB, Satwani P, Baldinger L, Morris E, van de Ven C, Del Toro G, Garvin J, George D, Bhatia M, Roman E, Baxter-Lowe LA, Schwartz J, Qualter E, Hawks R, Wolownik K, Foley S, Militano O, Leclere J, Cheung YK, Cairo MS. Bone Marrow Transplant. 2007;40:621-631.

The authors investigated reduced intensity umbilical cord blood transplantation (RI-UCBT) in 21 children and adolescents with malignant (n=14), and non-malignant diseases (n=7). RI conditioning consisted of fludarabine (150-180 mg/m2) with either busulfan (< or = 8 mg/kg)+rabbit antithymocyte globulin (R-ATG; n=16) or cyclophosphamide+R-ATG+/-etoposide (n=5). HLA matches were as follows: 4/6 (n=13), 5/6 (n=5) and 6/6 (n=3). The median total nucleated cell and CD34+ cell dose per kilogram were 3.58 x 10(7) and 2.54 x 10(5), respectively.

The median time for neutrophil and platelet engraftment was 17.5 and 52 days, respectively. There were six primary graft failures (chronic myelogenous leukemia (CML), beta-thalassemia, hemophagocytic lymphohistiocytosis (HLH) and myelodysplastic syndrome (MDS)). Five of the six patients had diseases that were not treated with chemotherapy or immunosuppressive therapy before RI conditioning. Four of these patients achieved full-donor chimerism after undergoing a second, but this time myeloablative UCBT.

The probability of developing grade II to grade IV acute graft-versus-host disease (GVHD) and chronic GVHD was 28.6 and 16.7%, respectively. The incidence of transplant-related mortality (TRM) was 14%. The 5 years overall survival (OS) in all patients was 59.8%. The 5 years OS for patients with average versus poor-risk malignancy was 77.8 versus 22.2% (P=0.03).

The authors concluded that RI-UCBT may result in graft failure in specific high-risk chemo-naïve patients (CML, beta-thalassemia, HLH and MDS), but in more heavily pretreated pediatric and adolescent recipients results in rapid engraftment and may be associated with decreased severe GVHD and TRM. The results need to be interpreted with caution because they were obtained with a heterogeneous group of patients and different RI conditioning regimens. A larger cohort of patients should be studied with much longer follow-up.

  1. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplant outcomes in 110 adults with hematological disease. Brunstein CG, Barker JN, Weisdorf DJ, Defor TE, Miller JS, Blazar BR, McGlave PB, Wagner JE. Blood 2007; 110:3064-3070.

This report establishes the safety profile of a nonmyeloablative treatment regimen consisting of fludarabine (FLU), cyclophosphamide (CY) and single fraction total body irradiation (TBI) in recipients of UCB in 110 consecutive adult patients with hematological disease. Ninety-three of the 110 patients received a double cord transplant.

Inclusion Criteria. Patients with advanced or high-risk hematologic disease were eligible for UCB transplantation if they had no related donor matched at 5-6/6 HLA loci (A, B, and DRB1). Patients were eligible for nonmyeloablative therapy if they met any of the following criteria: age >45 years, pre-existing high risk clinical features for TRM (serious organ dysfunction; invasive mold infection within 4 months prior to transplantation; Karnofsky Performance score 50-60 or history of extensive prior therapy [defined as: >12 months alkylator-based chemotherapy; >6 months alkylator-based chemotherapy plus extensive radiation; or history of autologous transplantation]).

UCB unit selection algorithm. UCB units were required to be matched at >4 of 6 HLA antigens based on antigen-level HLA-A and B typing and allele-level HLA-DRB1 typing. UCB units were required to have a minimum cryopreserved total nucleated cell (TNC) dose of 2.0 x 107/kg. However, the target cell dose was ≥3.0 x 107 TNC/kg resulting in the selection of a second partially HLA matched UCB unit if available. In those for whom a second UCB unit could be identified, the second unit also had to be 4 of 6 antigen matched with the first unit.

Treatment. 110 patients received a single dose of CY 50 mg/kg on day -6, FLU 40 mg/m2 daily on days -6 to -2, and a single fraction of TBI 200 cGy without shielding on day -1. ATG was given at 15 mg/kg every 12 hours on days -3 to -1 in a subpopulation of patients who had received less than two cycles of multiagent chemotherapy within the 3 months prior to enrollment (and no history of autologous transplantation.). All patients received CsA twice daily from day -3 for at least 3 months with target trough levels of 200-400 ng/ml and MMF at 1 g intravenously or orally twice daily from day -3 to +30.

Results. Most patients received two UCB units (n=93) to achieve the required cryopreserved cell dose. Neutrophil recovery was achieved in 92% at median of 12 days. Incidences of grades III-IV acute and chronic GVHD were 22% and 23%, respectively. Transplant-related mortality was 26% at 3 years. Survival and event-frees survival at 3 years were 45% and 38%, respectively.

Favorable risk factors were absence of high risk clinical features and absence of severe GVHD (p=0.04) for survival, and absence of high risk clinical features (p<0.01) and use of two UCB units (p=0.07) for event-free survival.

Discussion. The study supports the use of UCB transplantation after a non-myeloablative therapy in adults with hematologic disease. It is clear that the use of the double UCB platform in the setting of a nonmyeloablative therapy extends the availability of transplantation to those who cannot find a suitably HLA matched adult volunteer marrow or peripheral blood donor and who are at increased risk of regimen-related toxicity and transplant related mortality, such as older or heavily treated patients.

  1. Are 2 cords better than 1? Shpall E, De Lima M, Jones R, Champlin R. Blood. 2007;110:2789-2790.

(This article is a commentary on an article by Brunstein et al., (Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplant outcomes in 110 adults with hematological disease. Blood. 2007;110:3064-3070) In this study, most patients received two UCB units (n=93) to achieve the required cryopreserved cell dose. The Brunstein article is posted on the Cord Blood Forum in the Annotated Bibliography. See Topic IV, Reduced Intensity and Non-Myeloablative Transplants, i. Cord Blood Transplants, Citation #5.)

A major limitation of UCBT has been the small cell dose and resulting delayed time to engraftment in adults. The data in the report by Brunstein et al convincingly demonstrate that rapid neutrophil recovery with ultimate predominance of a single cord can be achieved using double cord blood transplants. Although the follow-up is short, the favorable relapse-free survival following a non-myeloablative regimen suggests a potent UCB-mediated graft-versus-tumor effect.

A single very large UCB unit meeting the protocol transplant standard was found and used in only 17 of the 110 patients, underscoring the limitations of comparing transplantation of 1 versus 2 cords in this study. Nevertheless, as suggested by the authors, it appears unlikely that a randomized comparison of unmanipulated single versus double UCBT will be performed for adults. Double UCBT seems likely to emerge as a standard to which newer adult UCBT techniques will be compared in the future.

The authors of this commentary go on to address a number of important questions that continue to surround double UCBT. An important one of these is that 2 cords may produce a somewhat higher incidence of acute GVHD which brings up the question of whether GVHD should be modulated using high-dose anti-thymocyte globulin (ATG) or similar techniques.

The authors conclude that the report of Brunstein et al., as well as other studies which they cite, provide increasing evidence that UCBT represents a practical and important advance in hematopoietic cell transplantation

  1. Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Ballen KK, Spitzer TR, Yeap BY, McAfee S, Dey BR, Attar E, Haspel R, Kao G, Liney D, Alyea E, Lee S, Cutler C, Ho V, Soiffer R, Antin JH. Biol Blood Marrow Transplant. 2007;13:82-89.

In an effort to increase the cell dose and decrease transplantation-related toxicity, the authors treated 21 adult patients (24-63 years) with a reduced-intensity conditioning regimen followed by sequential infusion of 2 partially matched umbilical cord blood (UCB) units. Two patients had aplastic anemia, one had myelodysplastic syndrome and the others had hematologic malignancies, the most common diagnosis being acute myeloid leukemia.

The reduced-intensity conditioning regimen consisted of fludarabine, melphalan, and antithymocyte globulin. The UCB units were a 4/6 HLA match or better with each other and with the patient and achieved a minimum precryopreservation cell dose of 3.7 x 107 nucleated cells/kg.

The median time to an absolute neutrophil count > 0.5 x 109/L was 20 days, and the median time to an unsupported platelet count > 20 x 109/L was 41 days. Two patients experienced primary graft failure and underwent a second UCB transplantation. One patient had a late graft failure. Acute graft-versus-host disease (GVHD) grade II-IV occurred in 40% of patients. The 100-day TRM was 14%, and the 1-year disease-free survival was 67%. Mixed chimerism was associated with a higher risk of chronic GVHD.

The authors concluded that their findings indicate that adult patients can tolerate double UCB transplantation well and achieve sustained antitumor responses using this reduced-intensity conditioning regimen.

8A. Successful engraftment in reduced-intensity cord blood transplantation (CBT) as a salvage therapy for graft failure after primary CBT in adults. Kawamori Y, Yakushijin K, Okamura A, Nishikawa S, Minagawa K, Shimoyama M, Yamamoto K, Katayama Y, Matsui T. Transplantation. 2007;83:1281-1282.

The authors stated that they performed a second CBT in four cases with primary graft failure after CBT and all cases successfully achieved engraftment.

Three points were emphasized. First, they tried to confirm graft failure and to make a decision to perform the salvage CBT as quickly as possible. The confirmation of graft failure was made by no donor chimerism in bone marrow cells on day 28 or by no sign of hematopoietic recovery until day 35 after primary CBT. Second, reduced-intensity CBT was chosen for the second transplant to avoid regimen-related toxicity and mortality. They used a fludarabine-based preparative regimen. Third, to intensify the immunosuppression in combination with a key drug tacrolimus, they utilized mycophenolate mofetil (MMF) instead of methotrexate. The authors add that it would be important to make sure of the availability of a cord blood unit for salvage transplant as early as possible.

[Note: The general principles put forward by this and the subsequent 4 papers are (1) Graft failure must be diagnosed expeditiously, (2) A search for a cord blood unit (or units) should be undertaken as soon as the possible need is identified, and (3) A reduced-intensity transplant is preferable in order to minimize transplant-related morbidity.]

8B. Second transplant with two unrelated cord blood units for early graft failure after haematopoietic stem cell transplantation. Fernandes J, Rocha V, Robin M, de Latour RP, Traineau R, Devergie A, Ribaud P, Réa D, Larghero J, Gluckman E, Socié G. Br J Haematol. 2007;137:248-251.

This is a report of four patients who developed early graft failure after unrelated HSCT and who subsequently received a double unrelated cord blood transplant after reduced-intensity conditioning, at a median 15 days after the decision to perform a second transplant. Neutrophil recovery was observed in all four patients between day +15 and +31 with full donor chimerism of one unit. Acute GVHD grades II-IV was observed in three patients. Three are alive, between 12 and 25 months after the double UCBT. The authors concluded that double UCBT is a promising procedure to treat early GF.

8C. Successful second cord blood transplantation using fludarabine and cyclophosphamide as a preparative regimen for graft rejection following reduced-intensity cord blood transplantation. Mizutani E, Narimatsu H, Murata M, Tomita A, Kiyoi H, Naoe T. Bone Marrow Transplant. 2007;40:85-87.

The authors describe 5 patients who had received a second CBT for graft rejection using a preparative regimen consisting of fludarabine and melphalan with or without TBI. Although 4 of the patients achieved engraftment, three ultimately died of transplant-related mortality. All 5 patients developed grades 3-5 regimen-related toxicities.

As a result of the above experience, the authors performed a reduced-intensity CBT using fludarabine and cyclophosphamide without TBI in a patient with initial graft rejection. The patient received the second transplant as treatment for the initial graft rejection 35 days after the initial CBT. The preparative regimen consisted of 125 mg/m2 fludarabine (day -6 to -2, 25 mg/m2/day) and 60 mg/kg cyclophosphamide on day -6. Prophylaxis for GVHD consisted of 0.02 mg/kg tacrolimus and short-term methotrexate (day 1, 10 mg/m2/day; days 3 and 6, 7 mg/m2/day).

The patient had HHV-6 encephalitis that resolved spontaneous and an invasive fungal infection that responded to antifungal therapy. She did not develop acute GVHD. Engraftment of neutrophils (>500/µL) occurred on day 19 and complete donor chimerism was achieved. Although the patient’s neutropenic period lasted 44 days, she did not develop fatal infectious complications. The bone marrow examination done on day 97 revealed normal hematopoiesis and complete donor chimerism.

The authors emphasize that rapid diagnosis of graft rejection and re-transplantation is important. In this patient graft failure was diagnosed on day 28 based on chimerism analysis of the bone marrow cells. However, monitoring of chimerism in the peripheral blood on a weekly basis might have helped to establish the diagnosis more rapidly.

8D. Successful engraftment of the second reduced-intensity conditioning cord blood transplantation (CBT) for a patient who developed graft rejection and infectious complications after the first CBT for AML. Nakamura Y, Tanaka Y, Ando T, Sato Y, Yujiri T, Tanizawa Y. Bone Marrow Transplant. 2007;40:395-396.

The authors state that there are limited data on the management of graft rejection that may follow CBT. In this report they describe the case of a patient who was successfully treated with a second reduced-intensity conditioning (RIC) CBT, despite the fact that he was suffering from serious infectious complications.

A 44 year-old-man with AML achieved CR with the first course of induction chemotherapy. However, he relapsed and achieved a second CR after the second course of chemotherapy. He received a CBT consisting of an infusion of a serologically two HLA-loci mismatched unrelated cord blood containing 2.20 x 107 nucleated cells/kg. On day +28 the BM sample revealed a severely hypocellular marrow and PCR analysis indicated complete recipient cells in the PBMC, and graft rejection was diagnosed. Simultaneously CMV and human herpesvirus 6 (HHV6) DNA were detected in the PBMC by real-time PCR; therefore, treatment using 60 mg/kg foscarnet per day was started. On day +34 bacteremia due to Stenotrophomonas maltophilia and endotoxemia developed. Immediate treatment was started with ciprofloxacin and minocycline and the central venous catheter was removed.

A second CBT was scheduled with the continuous administration of antimicrobial agents. The second CBT was also a serologically two-HLA-loci mismatched unrelated cord blood, and contained 2.26 x 107 nucleated cells/kg at an interval of 45 days from the first CBT. Despite additional infectious complications and grade I acute GVHD, he recovered. Five months after the second CBT he remains in CR with a Karnofsky performance status of 100%.

The authors chose an RIC regimen for the second CBT to minimize immunosuppression. Further, they point out that there are reports that the GVHD prophylaxis regimen using a calcineurin inhibitor and MMF is associated with faster engraftment, decreased incidence of mucositis, similar incidences of GVHD and comparable risk of infection as compared to using a c

8E. Severe regimen-related toxicity of second transplantation for graft failure following reduced-intensity cord blood transplantation in an adult patient. Shimada K, Narimatsu H, Morishita Y, Kohno A, Saito S, Kato Y. Bone Marrow Transplant. 2006;37:787-8.

To reduce regimen-related toxicity (RRT) for patients with graft failure, the authors employed a reduced-intensity conditioning regimen in which TBI was omitted.

A 65-year-old man with MDS underwent reduced-intensity CBT but peripheral cytopenia persisted after the transplant. Bone marrow examination on day 26 revealed severe marrow hypoplasia and 100% host chimerism. Graft rejection was diagnosed.

A second reduced-intensity CBT was performed with an interval of 34 days. The conditioning regimen consisted of fludarabine 150m/m2 + melphalan 80 mg/m2. Engraftment of neutrophils >500/µl was achieved on day 28 and the bone marrow examination showed complete donor chimerism. However, severe RRTs and hepatic veno-occlusive disease developed, and the patient died of multiorgan failure on day 30 after the second transplant.

The authors commented that this case indicates that, since their patient rapidly achieved full donor chimerism, TBI might not be necessary in conditioning regimens for a second reduced-intensity CBT. A reduced dose of melphalan, such as 60 mg/m2, could have ameliorated RRTs while ensuring engraftment.

In summary, reduced-intensity CBT is optimal for a second transplant following graft failure, but further studies regarding the optimal conditioning regimen are warranted. alcineurin inhibitor with MTX. Therefore, the authors selected the combination of tacrolimus and MMF.

  1. Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. Komatsu T, Narimatsu H, Yoshimi A, Kurita N, Kusakabe M, Hori A, Murashige N, Matsumura T, Kobayashi K, Yuji K, Tanaka Y, Kami M Ann Hematol. 2007; 86:49-54.

This is a report of a pilot study to evaluate the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen in adult patients with advanced hematologic malignancies.

The authors point out that optimal preparative regimens remain unknown in RI-CBT and that low-dose TBI is frequently added to overcome an HLA barrier. However, TBI might increase regimen-related toxicity, leading to a high risk of infection and/or organ dysfunction.

Seventeen patients with a median age of 58 years (range, 38-74) underwent RI-CBT at Tsukuba Memorial Hospital between April 2004 and November 2005. Preparative regimens were fludarabine 30 mg/m(2) for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of infused total nucleated were 2.6x10(7)/kg (range, 2.0-3.3). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigens (n=1).

Underlying diseases progressed despite preparative regimens in four patients. Of the remaining 13 patients, nine patients achieved engraftment at a median of day 18 (range, 17-28). Six of the nine patients with engraftment achieved complete donor-type chimerism by day 100. Six patients were alive in remission at median follow-up of 13.1 months (range, 1.0-19.0).

The authors concluded that adult patients with advanced hematologic malignancies and extensive history of chemotherapy can achieve engraftment even without TBI.

Omission of TBI diminishes the anti-tumor effect of the preparative regimen, while allogeneic immune reaction (graft-vs-tumor effect) appears late after transplantation. The present conditioning regimen may not be feasible for patients with a rapidly progressing disease at the beginning of the conditioning regimen When disease progression is controlled by the preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor effect.

  1. Comparable results of umbilical cord blood and HLA matched sibling donor hematopoietic stem cell transplant after reduced-intensity preparative regimen for advanced Hodgkin's lymphoma. Majhail NS, Weisdorf DJ, Wagner JE, Defor TE, Brunstein CG, Burns LJ. Blood 2006;107:3804-7.

The authors compared the safety and efficacy of allogeneic stem-cell transplantation after reduced-intensity conditioning (RIC) using either unrelated umbilical-cord blood (UCB) or matched-sibling donors (MSD) in 21 high-risk adults with advanced Hodgkin's lymphoma (UCB-9, MSD-12).

In this study RIC regimens were used for the following indications: (1) age >55 years with MSD (n=4), or age >45 with UCB donor (n=1), (2) extensive prior therapy (previous autologous stem cell transplant (n= 14), or >12 months of alkylator chemotherapy (n= 16), and/or (3) poor performance status including major co-morbidity (n= 6); 14 patients had two or more of these high-risk features.

UCB grafts had at least 4 of 6 HLA-A, B, DRB1 antigens that were matched to the recipient, and if two donor units were infused, to each other as well. Each unit had a cryopreserved cell dose of at least 1.5 x 107 nucleated cells per kilogram of recipient body weight. Seven of the nine patients (78%) receiving UCB grafts received two UCB units. The median infused cell dose wad 3.8 x 107 nucleated cells/kg.

Both groups were comparable except for younger age in UCB cohort (median 28 vs. 42 years, p=0.02). Neutrophil recovery occurred earlier in MSD group (median 7 vs. 10 days, p=0.02). All patients had sustained donor-engraftment by day +60. Cumulative incidence of acute severe graft-versus-host-disease (33% vs. 33%, p=0.99), chronic graft-versus-host-disease (11% vs. 33%, p=0.24) and 100-day treatment-related mortality (11% vs. 17%, p=0.80) were comparable. With a median follow-up of 17 and 24 months, the 2-year progression-free survival is 25% (95% CI, 0-55%) for UCB vs. 20% (95% CI, 0-44%) for MSD alloSCT (p=0.67).

The authors indicate that their results suggest comparable outcomes for reduced-intensity alloSCT using UCB or MSD source in high-risk adults with advanced Hodgkin's lymphoma.

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