Cancer Treatment Today » Acute Lymphocytic Leukemia

Velcade for Graft Vesus Host Disease

M Levin, MD — Wed, 01 Jan 2014 18:10:42 +0000

Shen transplanted from an immunologically different person, graft cells can attack the host’s body. This is called Graft Versus Host Diseas*GVHD)e and remains a serious problem in transplantation. One trial by Koreth and others found that Velcade was beneficial in GVHD; but his was a phase II trial other phase II trials are ongoing. Koreth treated 45 patients; 89% of patients who were treated had a one-locus and 11% of patients were treated with a two-loci mismatch. With a median follow-up of 3 years, the 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22%, and the 1-year cumulative incidence of chronic GVHD was 29%. The non-relapse mortality rate was only 11%, and the relapse rate was 38%. Results were comparable with patients who received HLA-matched transplants with the unexpected observation that bortezomib therapy enhanced immune reconstitution of CD8+ T cells and natural killer cells.
The editorial by Giralt that accompanied Koreth report, pointed out that there are four potential approaches to developing treatments for GVHD problem and that it may be necessary to perform a randomized phase II trial with a short primary end point to be able to rapidly pick a winner from among these competing approaches that could be compared with the current standard in a definitive trial.

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Allogeneic stem cell transplantation in childhood ALL

M Levin, MD — Fri, 24 Aug 2012 16:51:50 +0000

Acute Lymphocytic Leukemia(ALL) is the most common cancer diagnosed in children and represents almost 25% of cancers in children younger than 15 years. Complete remission of disease is now typically achieved with pediatric chemotherapy regimens in approximately 95% of children with ALL, with up to 85% long-term survival rates. Interestingly, recent studies appears to show that young adults with ALL do better with pediatric regimens and specifically adult ones. Unfortunately, those who relapse after initial treatment have few good options and retreatment rarely produces a cure.

Three randomized controlled trials (RCTs) that compared outcomes of hematopoietic sibling stem cell transplantation(SCT) to outcomes with conventional-dose chemotherapy in children with ALL did not demonstrate superiority of transplantation in all comers but did suggest that those at high risk for relapse or those in relapse who were able to obtain another remission, did better. The literature in general shows promising results for allogeneic SCT in patients in first complete response at high risk for recurrence, and in patients in second or greater remission. This conclusion is further supported by an evidence-based systematic review of the literature sponsored by the American Society for Blood and Marrow Transplantation (ASBMT)(Hahn et al). Outcomes following matched unrelated donor and umbilical cord blood transplants have improved significantly over the past decade and may offer outcome similar to that obtained with matched sibling donor transplants.

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Repeat Allogeneic Stem Cell Transplantation for ALL

M Levin, MD — Tue, 17 Jul 2012 16:13:41 +0000

ALL is the most common cancer diagnosed in children and young adults, represents almost 25% of cancers in children younger than 15 years. Complete remission of disease is now typically achieved with pediatric chemotherapy regimens in approximately 95% of children with ALL, with up to 85% long-term survival rates. Young adults are treated as children, but the relapse rate is higher. Allogeneic stem cell transplantation is an important salvage option for those who don’t respond. But what happens when ALL comes back after a transplant?

Relapsed patients can re-transplanted, receive Donor Lymphocyte Infusions or go into clinical trials. How good of a choice is re-transplanting?

O’Brien looked at 288 patients who received second salvage therapy for ALL and found that they have a poor prognosis. It is tempting to re-transplant patients who relapse despite having had an allogeneic transplant But results are not impressive. A second BMT results in long-term event-free survival in only 10–20% of patients with relapsed ALL. It is true that most patients who relapsed after a transplant are not great candidates for a repeat transplant. Only 7–20% of patients have been reported to reach the stage of a second BMT after relapse according to the performance and remission status after salvage chemotherapy. Moreover, second BMT is associated with extremely high treatment-related mortality, ranging from 40% to 50%.

Thus, the outlook for patients with post-transplant relapse of acute leukemia is extremely poor; currently, no single therapy consistently results in durable remissions. There are no guidelines recommending a second allogeneic transplant and it is hard to see why a stem cell transplant would work better a second time around unless something different is done.

Read the Professional version here.