Stem Cell Transplant — Calculating the Odds

 Stem Cell Transplant –The odds of a successful outcome…

Due to risk factors and associated economic, social and physical challenges, there is, perhaps, no more momentous decision a myeloproliferative neoplasm (MPN)  patient has to make than to elect a stem cell transplant (SCT).  Despite some promising medical interventions SCT remains the single curative  MPN option. 

  For some, in high risk status, faced with dangerously accelerating signs of disease progression, there is little choice. For others, the timing of an SCT is largely elective.

The prospect of a stem cell transplant (SCT) is never far from an MPN patient’s mind.  At first diagnosis the idea arises as a possibility to nip this disease in the bud, get a fresh start at producing healthy blood lines. For those with myelofibrosis, the acute phenotype of MPN, SCT can appear to be our only option to stop progression once surging counts are brought under control.

There are  real hurdles: Finding a transplant team, locating a compatible donor, arranging insurance coverage , preparing for the rigorous Induction procedure, arranging for temporary housing, family support, etc. The one overwhelming question is deciding whether and when to elect the procedure.. Finally, however, it is up to each of patient alone —  with the support of her or his hematologist — , to make this life-altering decision.

According to Professor. Ruben Mesa,MD (UT Health San Antonio MD Anderson)  “Anyone who tells you that the issue of whether or not to have a bone marrow transplant is a simple decision is an individual not facing that decision.”

The Goldilocks Moment

After the decision to proceed with an SCT has been made, the key question is timing.  To elect the procedure too early might mean,, in some cases, the loss of quality time to induction,  recovery and a protracted struggle with Graft Versus Host Disease.  To start down the SCT road too late might mean facing the onset of AML or other complications making a successful outcome less likely.

A proven SCT maxim: The younger and stronger a patient, the greater the odds of success.

MPN patients have undertaken their stem cell transplant procedure at an early disease stage and are living long MPN-free lives with the need for drugs, transfusion or other therapeutic interventions.  The more common option is for patients to enjoy a relatively high quality of life and wait until an SCT is clearly indicated.

The Goldilocks SCT Moment arrives as a myelofibrosis patient enters into a high risk status but is still young and strong enough to negotiate the rigors of induction and recovery.

“In a matched analysis of patients with PMF treated with transplantation or conventional therapy in the preruxolitinib era, patients with intermediate 2 risk and high risk according to DIPSS showed improved survival after transplantation, whereas low-risk patients benefitted more likely from a nontransplant approach and intermediate-1-risk patients were in favor neither for transplant nor for a nontransplant approach.” Kroger et al,

MAGIC and Risk Assessment.

Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation…  Here is a prognostic score to determine prognosis after transplantation itself. A German-French study using clinical, molecular and transplant-specific informaiton from a total of 361 myelofibrosis patients.

Several scales have evolved and been clinically tested to determine to determine who among patients with myelofibrosis should be referred to transplantation.  To assist patients and their hematologists in this process the MPN Research Foundation funded the MAGIC project, a multi-disciplinary  online graphic representation of results from key validated scales, the DIPSS and DIPSS Plus>

The International Prognostic Scoring System (IPSS) is valid for newly diagnosed primary MF patients, whereas the dynamic IPSS (DIPSS) can be used at all times of the disease course. The IPSS and DIPSS both include 5 independent variables predicting survival (age >65 years, hemoglobin <10 g/dL, leukocytes >25 × 109/L, circulating blasts ≥1%, and constitutional symptoms)

The DIPSS-plus score also considered 3 additional prognostic factors (transfusion-dependence, platelet count <100 × 109/L, and unfavorable karyotype).

Other scales, eg the Mutation-Enhanced System (MIPSS70)  included significant mutations – ASXL1, EXH2, SRSF2, ISH1/2 –( See Notes on MPN Mutations for further description.)  — as well as the number of these high risk mutations.  For patients with post-ET/PV myelofibrosis the  (MYSEC-PM) was developed.

However, useful these scales have proven in determinaton of risk status and SCT tming they did little to predict outcome after transplantation itself

The MTSS –Myelofibrosis Transplant Scoring System.

“Here,”” says Kroger et al., ” we aimed to develop a comprehensive clinical-molecular model for myelofibrosis to predict outcome after stem cell transplantation, which may allow proper counseling regarding patients’ posttransplant prognosis.”

Kroger’s German-French group  developed a comprehensive clinical-molecular myelofibrosis transplant scoring system (MTSS).  Variables associated with overall survival (OS) analysis were selected and then, subsequently, used to construct a multivariable model such as Karnofsky performance status (The Karnofsky Performance Scale (KPS) is an assessment tool for predicting the length of survival in terminally ill patients. The KPS is an 11 point rating scale which ranges from normal functioning (100) to dead (0) in ten point increments) spleen status before transplantation, time between diagnosis and transplantation, stem cell graft source, and donor source (HLA-matched related, matched unrelated, mismatched, etc.


Some additional resources:

On stem cell transplant: An  Interview with Dr. Nicolaus Kroger

Considering stem cell transplant – Answers to common patient questions plus a Roundtable Discussion
This Roundtable consists of introductory answers to common patient questions by Dr. David Steensma and Dr. Claire Harrison followed by panel discussion of these and related issues. 

Participating in the Roundtable discussion are Dr. Donal McLornan, Dr. Nicolaus Kroger, Dr. Tsiporah Shore, Dr . Srdan Verstovsek,  Dr. Vena Fauble, Dr, Ruben Mesa, Dr. Richard Silver, Dr. Claire Harrison. The Roundtable concludes with the patient’s perspective provide by Chris Harper, a short reflection on the underlying biology, and a video featuring Dr. Ruben Mesa and Dr. Veena Fauble.

Stem Cell Transplantation  — The basics of stem cell transplantation from the Leukemia & Lymphoma Society.

Stem Cell Transplant…What happens. The ABCs of stem cell transplant from the UK’s National Health Service, outlining testing, harvesting of stem cells, patient conditioning prior to transplant, the transplantation process itself and the recovery period.

SCT — Front line reports-An extensive presentation of opinion, fact and stories surrounding stem cell transplant.   MPN patients sharing their stories, MPN and transplant specialists answering questions, science, charts and data from primary sources, video…and links to key stories.

This is a fairly a comprehensive  guide to the stem cell transplant experience for those who now, or in the near future, may be entering that world.   It is a miniature resource library that may be  scanned, bookmarked, and reviewed as needed.