“High dose” Chemotherapy with hematopoietic stem cell transplantation - Jean-Pierre Lotz, MD, PHD

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JEAN-PIERRE LOTZ, MD, PHD


This highly technical therapeutic approach is aimed at certain tumors that have recurred or that have become completely resistant to standard treatments.

It is comprised of three steps:

  1. in the first step, hematopoietic stem cells are extracted from the patient’s blood.  These are cells from which all blood cells (white, red, platelets) are constantly renewed.  These hematopoietic stem cells reside mainly in the bone marrow, from which in the past we used to retrieve them (whence the term “marrow graft” for a series of operations), but a certain number of them circulate in the blood from which it is much easier to extract them;
  2. in a second step, the patient receives a very high dose of chemotherapy, which overwhelms the tumor’s resistance, but which also leads to a dramatic reduction in levels of white and red blood cells and platelets, which presents major risks to the patient;
  3. in the third step we re-inject  the patient his own hematopoietic stem cells which have been stored out of  the chemotherapy damage.  These stem cells restore the normal blood cells that were destroyed by chemotherapy along with the tumor cells, and in particular increase the white cells essential to fighting off infections.  Thus we avoid the dangerous hematological toxicity from the high doses of chemotherapy, without any risk of rejection of the “graft,” since it consists of the patient’s own cells.

To increase the patient’s chances of being cured, we can sometimes apply this type of intensive therapy in two successive sessions (double self-graft) or three times (triple self-graft).

Our team was one of the first three in the world, along with teams from New York and Indianapolis, to develop this technique; our work is known throughout the world, and is regularly cited.  In 25 years of experience, closely involved in national and international trials, more than 1,500 intensive therapies have been carried out in the sterile intensive care section of the clinical oncology and cell therapy units of Tenon Hospital.

At present, it is primarily for patients afflicted with testicular tumors not responding to conventional treatments that this type of intensive therapy is prescribed.  Our unit is internationally one of the most experienced with this therapeutic approach to “high dose” chemotherapy with double or triple self-grafts administered to young, and even very young patients whose life prognosis is threatened.

Hello,

My name is Jean-Pierre Lotz.  Since 2002 I have been the medical director of the clinical oncology and cell therapy unit at Tenon Hospital, part of an extensive group of university hospitals.  I am also the president of the Scientific Board of APREC. When introducing the clinical oncology and cell therapy unit, I emphasize the term “cell therapy.” Indeed,  this unit is unique in that it has something not found in other clinical oncology departments in France: it is a combination of both an intensive patient care unit and of a cell therapy unit.  And this is where APREC plays a particularly important role, because since 1987 that organization has been entirely devoted to treating extremely serious pathologies, and has enabled the treatment of more than 1,000 patients within extremely particular programs.

From the beginning APREC has been closely involved with the European Group for Blood   Marrow Transplantation (EBMT), and with a French organization, the “ Fédération Nationale des Centres de Lutte contre le Cancer” (National Federation of Centers Fighting against Cancer).

In fact, we have been involved in very wide-reaching projects, dealing with a great number of pathologies, such as breast cancers, ovarian cancers, sarcomas of the soft tissue, osteosarcomas — all extremely serious diseases — and above all testicular tumors. Usually testicular tumors are extremely curable forms of cancer.  There are some famous examples of this, notably in the world of sports. But not all of these young patients can be cured; 20% of them cannot be cured simply with conventional chemotherapy. Those patients are then referred to us so that they may undergo very intensive and complex chemotherapies, each one of these requiring to be followed by a rescue treatment using hematopoietic stem cells that have been previously taken from the patient’s blood. These stem cells restore, through the restoration of the patient’s bone marrow, the white blood cells which have been totally destroyed by the intensive chemotherapy.These patients are hospitalized in very specific conditions.  APREC has played a major role here, since through that organization, through the structuring of clinical research, we have been directly involved in every project of intensive chemotherapy in France.  Everyone remembers the PEGASE protocols, for example, and we were at the international forefront of those protocols.

For various and complex reasons, our work has today centered around a single pathology – we are focused on the treatment of young patients afflicted with testicular cancer not responding to conventional treatments,  and APREC, here too, has played an important role. It initiated three protocols called TAXIF I, TAXIF II, and TAXIF III.   The first has been published, the second is in production, and the third is in process.  What is important is that we have been recognized as a particularly advanced center because these protocols have all been designated PHRC (Programme Hospitalier de Recherche Clinique – national Hospital Protocol of Clinical Research), that is, supported financially by the government as a national project in clinical research.

Since the beginning of this work, we have, in fact, carried out more than 1,500 intensive therapies, leading us to treat patients throughout France, and also, as will soon be the case, patients from around the world.

All of this would not have been possible if – behind this clinical work – there hadn’t been a great deal of research, analysis of patients’ data, overseeing of treatments, etc., this is the role played by APREC.