Haploidentical versus Matched-Sibling Transplant in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia: A Biologically Phase III Randomized Study

Abstract

Purpose: Although matched-sibling donor (MSD) hematopoietic stem-cell transplantation (HSCT) has an established role in the management of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1), the effect of haploidentical donor (HID) HSCT as post-remission treatment for this portion of patients is not defined.Experimental Design: Transplantation outcomes from HIDs or MSDs were compared in a disease-specific, biologically phase III randomized, multicenter study. Between July 2010 and December 2013, 210 patients with Philadelphia-negative highrisk ALL in CR1 were assigned to undergo unmanipulated HIDs (121 patients) or MSDs HSCT (89 patients) according to donor availability on an intent-to-treat (ITT) basis.Results: Overall, 24 of the 210 patients had lost transplant eligibility. Therefore, 186 of 210 (88%) patients were finally transplanted from MSD (n ¼ 83) or HID (n ¼ 103). Based on the ITT principle, the 3-year disease-free survival (DFS) did not differ between HID and MSD groups [61%, 95% confidence interval (CI), 52%-70%; vs. 60%, CI, 49%-71%; P ¼ 0.91] from CR, neither did DFS differ between the two groups (68%, CI, 58%-78%; vs. 64%, CI, 52%-76%; P ¼ 0.56) from time of the graft, with cumulative incidence of nonrelapse mortality of 13% (CI, 7%-19%) and 11% (CI, 4%-18%; P ¼ 0.84) and relapse rates of 18% (CI, 10%-26%) and 24% (CI, 14%-34%; P ¼ 0.30), respectively.Conclusions: Haploidentical HSCT achieves outcomes similar to those of MSD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation could be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor.

Perianal Infections in the Phase before Engraftment after Allogeneic Hematopoietic Stem Cell Transplantations: A Study of the Incidence, Risk Factors, and Clinical Outcomes

“…Although the conditioning regimen for haplo-RD and URD HSCT was more intense than for ISD HSCT, several studies observed that the safety was similar in ISD and alternative donor HSCT recipients [7,19,20]. In addition, all the patients received sitz baths, had their perianal areas cleaned with 0.0005% iodophor solution after defecation, and received 2% iodoform-vaseline to protect the perianal skin.…”

Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation

“…66,[79][80][81][82][83][84][85][86] Therefore, lack of an HLA-matched donor does not preclude favorable transplantation outcomes. …”

“…85 A randomized, multicenter study in 210 patients with Philadelphia-negative ALL in CR1 showed 3-year disease-survival was ;65% after matched sibling and haploidentical transplantation. 86 Albeit nonrandomized, these studies suggest equivalence of haploidentical transplantation with matched sibling and unrelated donor transplantation.…”

A review of hematopoietic cell transplantation in China: data and trends during 2008–2016

“…7-10 However, current clinical practice is supported by the results of HID HCT and clinical trials organized by Huang et al (some trials are listed in Table 1). [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The AML patient subgroup classified in the low-risk karyotype by the World Health Organization stratification system, obtained benefit from allogeneic HCT in CR1 status following re-stratification by applying risk-directed therapy based on MRD. In a trial registered at http://www.chictr.org.cn/enIndex.aspx as #ChiCTR-OCH-12002406, 13 the high-risk group was defined as those patients not achieving major molecular remission (MMR) after the second consolidation therapy or those exhibiting the loss of MMR within 6 months of achieving MMR.…”