Treatment


There is no internationally accepted treatment protocol for JMML. Currently, three clinical treatment protocols are most widely used to study JMML and improve treatment for these children, and these are geographically-based:
  • North America: The Children’s Oncology Group (COG) ASCT1221 JMML Study (opened June 2013). 
**NEW!!!  Click here for a simplified description of this new and important COG trial ***

  • Europe: The European Working Group of Myelodysplastic Syndromes in Childhood (EWOG-MDS) studies: EWOG-MDS 2006 (opened January 2006)
*** NEW!!!  Click here for information on a new drug-based EWOG-MDS clinical trial (ITCC-015/EWOG- MDS-Azacytidine-2010) available for newly-diagnosed JMML patients in Europe *** 

  • Japan: The Japanese Leukemia Study Group (JPLSG) JMML-11 trial (opened July 2011).
*** NEW!!!  Participating facilities in Japan
    Other clinical trials open to patients with JMML may be searched for at the NIH Clinical Trials website or the European Union Clinical Trials Register.  Institutions and physicians treating JMML can be found on the JMML Specialists and Treatment Centers world map on our website (note: this map is not comprehensive but is provided as a starting reference point).


    The following procedures are used in one or both of the current clinical trials listed above:
    • Chemotherapy/Pharmacologic Treatment
    The role of chemotherapy against JMML before bone marrow transplant is unclear as no pre-transplant chemotherapeutic agent has shown clear activity in improving transplant outcomes. Chemotherapy alone has proven unable to bring about long-term survival in JMML.
    Low-dose conventional chemotherapy:
    • Studies have shown no influence from low-dose conventional chemotherapy on JMML patients’ length of survival.
    • Some combinations of 6-mercaptopurine with other chemotherapy drugs have produced results such as decrease in organ size and increase or normalization of platelet and leukocyte count.
    Intensive chemotherapy:
    • Complete long-term remission from JMML has not been possible through use of intensive chemotherapy, but it is still used at times because it has improved the condition of a small but significant number of JMML patients who do not display an aggressive disease.
    • The COG JMML Study recommends 2 cycles of fludarabine and cytarabine for 5 consecutive days along with 13-cis retinoic acid during and afterwards.
    • The EWOG-MDS JMML Study, however, does not recommend intensive chemotherapy before bone marrow transplant.
    • Radiation/Radiotherapy
    Radiation to the spleen does not generally result in a decrease in spleen size or reduction of platelet transfusion requirement and is not recommended.
    • Hematopoietic Stem Cell Transplantation (a.k.a. bone marrow transplant)
    The only treatment that has resulted in cures for JMML is a bone marrow transplant, with a 50-60% survival rate.

    The risk of relapsing after transplant is high, and has been recorded between 30 and 50% depending on patient risk factors.

    Generally, JMML clinical researchers recommend that a patient have a bone marrow transplant scheduled as soon as possible after diagnosis. For some specific gene mutations (in CBL, KRAS, or NRAS genes) physicians may wait to see if the disease spontaneously remits, but it is advised to have a transplant donor ready.

    A younger age at diagnosis predicts for better outcome.

    Donor:
    • Transplants from a matched family donor (MFD), matched unrelated donor (MUD), and matched unrelated umbilical cord blood donors have all shown similar relapse rates, though transplant-related deaths are higher with MUDs, mostly due to chronic graft-versus-host disease (GVHD) and the immunosuppressive medication that contributes to infections.
    • JMML patients are justified for MUD transplants if no MFD is available due to the low rate of survival without a bone marrow transplant.
    Conditioning regimen:
    • In Europe, the EWOG-MDS JMML treatment protocol includes busulfan cyclophosphamide and melphalan in its conditioning regimen.
    • In Japan, the JPLSG treatment protocol utilizes busulfan, fludarabine and melphalan
    • In the US, the COG JMML treatment protocol utilizes busulfan and fludarabine, with post-transplant sirolimus
    Graft versus leukemia:
    • The graft-versus-leukemia effect has been shown to play an important role in curing JMML. Evidence of either acute or chronic GVHD is linked to a lower relapse rate in JMML.
    • Careful management of immunosuppressant drugs for control of GVHD is essential in JMML; importantly, children who are weaned from immunosuppressant drugs earlier have a lower relapse rate.
    • After bone marrow transplant, reducing ongoing immunosuppressive therapy has worked successfully to reverse the course of a bone marrow with a dropping donor percentage and to prevent a relapse. Donor lymphocyte infusion (DLI), on the other hand, has not been very successful in bringing children with JMML back into remission.
    For more information on Bone Marrow Transplants, see the National Marrow Donor Program's article on "When Your Child Needs a Transplant".
    • Relapse
    After bone marrow transplant, the relapse rate for children with JMML is reported to be ~30%.

    Relapse often occurs within a few months after transplant and the risk of relapse drops considerably at the one-year point after transplant.

    A significant number of JMML patients do achieve complete remission and long-term cure after a second bone marrow transplant, so this additional therapy should always be considered for children who relapse.

    *** NEW!!! Click here for information on an EWOG-MDS clinical trial (ITCC-015/EWOG-MDS-Azacytidine-2010) available for relapsed JMML patients in Europe ***


    If you need help with some of the medical terms included in these pages, please use the NIH MedlinePlus Medical Dictionary

    The information on this page was last reviewed in January 2013 by Dr. Christian Flotho, Division of Pediatric Hematology and Oncology, University of Freiburg, Freiburg, Germany.

    Last update:  12/5/2014 by Fred Dini

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