Comparison of Outcomes of HLA-Matched Related, Unrelated, or HLA-Haploidentical Related Hematopoietic Cell Transplantation following Nonmyeloablative Conditioning for Relapsed or Refractory Hodgkin Lymphoma

141

Twenty-six patients with advanced Hodgkin's disease received a related HLA haploidentical unmanipulated BMT, following a nonmyeloablative conditioning with low-dose TBI, proposed by the Baltimore group; GvHD prophylaxis consisted of high-dose posttransplantation CY (PT-CY), mycophenolate and a calcineurin inhibitor. All patients had received a previous autograft, and 65% had active disease at the time of BMT. Sustained engraftment of donor cells occurred in 25 patients (96%), with a median time to neutrophil recovery (40.5 Â 10 9 /L) and platelet recovery (420 Â 10 9 /L) of þ 18 and þ 23 days from BMT. The incidence of grade II-IV acute GVHD and of chronic GVHD was 24% and 8%, respectively. With a median follow-up of 24 months (range 18-44) 21 patients are alive, 20 disease free. The cumulative incidence of TRM and relapse was 4% and 31%, respectively. The actuarial 3-year survival is 77%, the actuarial 3-year PFS is 63%. In conclusion, we confirm that high-dose PT-CY is effective as prophylaxis of GVHD after HLA haploidentical BMT, can prevent rejection and does not appear to eliminate the allogeneic graft versus lymphoma effect.

Section: Introductionmentioning

confidence: 99%

Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma

Raiola

Dominietto

Varaldo

et al. 2013

141

“…60,61,67 Three recent publications focused on the use of alternative donors and contributed to outline the role of HLA matching on outcome. [68][69][70] These data underline the feasibility of RIC allo-HCT and suggest searching for a suitable donor, either a MRD or an alternative one, as soon as relapse after an auto-HCT occurs.…”

Section: Monoclonal Antibodiesmentioning

confidence: 85%

Managing Hodgkin lymphoma relapsing after autologous hematopoietic cell transplantation: a not-so-good cancer after all!

Kharfan‐Dabaja

Hamadani

Sibai

et al. 2014

Hodgkin lymphoma (HL) relapsing after an autologous hematopoietic cell transplant (HCT) poses a therapeutic challenge. In this setting, salvage chemotherapy (for example, gemcitabine-based, ifosfamide-containing and others) or immunotherapy (for example, brentuximab vedotin) is essential as a bridging-cytoreduction strategy to an allogeneic HCT. Myeloablative allogeneic hematopoietic cell transplantation in relapsed HL is associated with high rates of non-relapse mortality. In carefully selected patients with chemosensitive disease, allografting following lower-intensity conditioning regimens can provide durable disease control rates of about 25-35%. Promising early results with haploidentical and umbilical cord transplantation are noteworthy and are expanding this procedure to patients for whom HLA-matched related or unrelated donors are not available. Unfortunately, a significant number of HL patients relapsing after an autologous HCT are not candidates for allografting because of the presence of resistant disease, donor unavailability or comorbidities. Brentuximab vedotin is approved for HL relapsing after a prior autograft. Rituximab and bendamustine are also active in this setting, albeit with short durations of remission. Histone deacetylase inhibitors (for example, panobinostat, mocetinostat), mTOR inhibitors (for example, everolimus) and immunomodulatory agents (lenalidomide) have shown activity in phase II trials, but currently are not approved for this indication. Second autologous HCT are rarely performed but this approach should not be considered standard practice at this time. The need for effective agents for post autograft failures of HL largely remains unmet. Continuous efforts to ensure early referral of such patients for allogeneic HCT or investigational therapies are the key to improving outcomes of this not-so-good lymphoma.

“…22 This benefit has been difficult to prove clinically, as there are no prospective randomized trials evaluating the antitumor efficacy of haploidentical HCT compared with matched related or unrelated donor stem cell transplants. Surprisingly, a higher relapse probability was observed in a retrospective analysis of the outcomes of transplants from T cell-depleted related and unrelated donors, one Agmismatched donors and haploidentical related donors by Drobyski et al 23 On the other hand, Burroughs et al 24 showed that relapse probabilities were lower following nonmyeloablative low-dose TBI-based haploidentical non-T cell-depleted SCT than HLA-matched related or unrelated donor HCT. Given the higher risk of GVHD following haploidentical HCT and the frequent need for aggressive immunosuppressive therapy to treat the GVHD, it is possible that much of the antitumor effect is abrogated by this potent immunosuppressive therapy.…”

Section: Haploidentical Hematopoietic Cell Transplantationmentioning

confidence: 99%

The great debate: haploidentical or cord blood transplant

Ballen

Spitzer

2010

One of the truly revolutionary advances in hematopoietic cell transplantation (HCT) is the increasingly successful use of alternative donors, thereby allowing the delivery of a potentially curative transplant to B75% of patients who do not have an HLA-matched sibling donor. A substantial proportion of the need has been met by HLA-matched volunteer unrelated donors, but an unmet need still exists, particularly among minority populations and for people who need a more immediate source of hematopoietic cells. Two such sources, umbilical cord blood (UCB) and haploidentical related donors, have filled most of this need, and outcomes following transplants from these donor sources are very promising. UCB has the advantages of ready availability and is less capable of causing GVHD but hematological recovery and immune reconstitution are slow. Haploidentical HCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post transplant cellular immunotherapy, but is complicated by a high risk of GVHD and poor immune reconstitution when GVHD is prevented by vigorous ex vivo or in vivo T-cell depletion. This review will discuss the pertinent issues that affect the choice of one donor source over another and offer recommendations regarding the optimal utilization of these donor sources. Bone Marrow Transplantation (2011) 46, 323-329; doi:10.1038/bmt.2010; published online 1 November 2010 Keywords: haploidentical transplant; cord blood transplant; alternative donors; GVHD IntroductionOnly 30% of patients have a matched sibling donor, and therefore the majority of patients who need an allogeneic transplant will need to find alternative hematopoietic cell sources. The National Marrow Donor Program and its cooperative international registries boast an estimated 12 million volunteer donors. It is estimated that B60% of Caucasian patients will be able to find a suitably matched unrelated donor and proceed to transplant. The outlook is worse for African-American patients and other minorities -African Americans represent 12% of the US population, but only 5% of unrelated transplants. Therefore, an estimated 5000 patients yearly are candidates for either a mismatched related donor (haploidentical), umbilical cord blood (UCB) or mismatched unrelated donor transplant. This review will focus on adults, and the advantages and disadvantages of the haploidentical and UCB approaches.Haploidentical and UCB hematopoietic cell transplants (HCTs) have never been compared in a randomized fashion. In general, haploidentical HCTs are cheaper and easier to schedule, but may be associated with a higher risk of graft failure and GVHD. UCB, especially use of double UCB rather than single UCB units, are expensive and have a high risk of infection; however, the risk of severe GVHD is low. There may be some subgroups of patients (based on disease, match, and so on) who might be better served by one graft source over another. In this paper, we will review the clinical outcome data for each approach...