Randomized clinical trials for hematopoietic stem cell transplantation: lessons to be learned from the European experience

Autologous hematopoietic stem cell transplantation (AHSCT) to treat multiple sclerosis (MS) has mostly been used in devastating cases as the last option to stop further neurological deterioration. However, evidence from several retrospective clinical trials indicates that young, less disabled patients with highly inflammatory active MS are the most likely to benefit from AHSCT, and after moving from high-intensity to nonmyeloablative procedures the tolerability of AHSCT has increased and its associated risk and mortality have declined considerably. Recent meta-analyses and randomized clinical trials show that AHSCT is more effective than currently approved disease-modifying therapies (DMTs), with suppression of disease activity in 70–90% of patients and long-term cessation of disease activity in two-thirds of treated patients. The rationale for AHSCT is to eliminate autoimmunity and achieve immune resetting by intense immunosuppression followed by infusion of autologous hematopoietic stem cells. Similar effects on the immune system have been suggested for cladribine and alemtuzumab treatment and, together with AHSCT, they constitute the induction or immune-reconstitution therapies for MS. Although, further randomized controlled trials of AHSCT for MS are needed, it has become clear that improved patient selection and lower intensity conditioning regimens have reduced AHSCT associated risks and mortality and strengthened the position of AHSCT among other DMTs. Do we have enough experience and scientific support for AHSCT in MS to move from an exclusive treatment for aggressive, treatment-resistant MS and acquire broader indications, similar to other effective DMTs?

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A Randomized Trial of Two 2-Dose Influenza Vaccination Strategies for Patients Following Autologous Hematopoietic Stem Cell Transplantation

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1711 ◽

2020 ◽

Author(s):

Benjamin W Teh ◽

Vivian K Y Leung ◽

Francesca L Mordant ◽

Sheena G Sullivan ◽

Trish Joyce ◽

...

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Influenza Vaccination ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Influenza B ◽

High Dose ◽

Hematopoietic Stem

Abstract Background Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. Methods A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post–first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. Results Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P > .05), and 78.8% and 97.1% for influenza-B/Yamagata (P = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2–14.9; P = .02). Conclusions High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. Clinical Trials Registration Australian New Zealand Clinical Trials Registry: ACTRN12619000617167.

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Reporting of adverse event data in hematopoietic stem cell transplantation clinical trials involving investigational new drugs or devices: A report from the William Guy Forbeck Foundation 2001 focus meeting on clinical trials in hematopoietic stem cell transplantation

Biology of Blood and Marrow Transplantation ◽

10.1053/bbmt.2002.v8.pm12108915 ◽

2002 ◽

Vol 8 (6) ◽

pp. 295-302

Author(s):

Paul J Martin ◽

Joseph H Antin ◽

Daniel J Weisdorf ◽

Virginia Paton ◽

Mary M Horowitz

Keyword(s):

Clinical Trials ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

New Drugs ◽

Event Data ◽

Hematopoietic Stem ◽

Adverse Event Data

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Perspectives on the co-treatment with GnRHa in female patients undergoing hematopoietic stem cell transplantation

Endocrine Connections ◽

10.1530/ec-17-0246 ◽

2017 ◽

Vol 6 (8) ◽

pp. R162-R170 ◽

Cited By ~ 3

Author(s):

Luminita Nicoleta Cima ◽

Anca Colita ◽

Simona Fica

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Randomized Clinical Trials ◽

Conditioning Regimen ◽

High Dose ◽

Hematopoietic Stem ◽

Gonadal Dysfunction

Outcomes after hematopoietic stem cell transplantation (HSCT) for patients with both malignant and nonmalignant diseases have improved significantly in recent years. However, the endocrine system is highly susceptible to damage by the high-dose chemotherapy and/or irradiation used in the conditioning regimen before HSCT. Ovarian failure and subsequent infertility are frequent complications that long-term HSCT survivors and their partners face with a negative impact on their QoL. Several meta-analyses of randomized clinical trials showed that gonadotropin-releasing hormone agonist (GnRHa) administration in advance of starting standard chemotherapy decreases the risk of gonadal dysfunction and infertility in cancer patients, but GnRHa use for ovarian protection in HSCT patients is not fully determined. In this review, we are discussing the potential preservation of ovarian function and fertility in pubertal girls/premenopausal women who undergo HSCT using GnRHa in parallel with conditioning chemotherapy, focusing on the current data available and making some special remarks regarding the use of GnRHa.

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