Fludarabine IV infusion over 30 minutes on D-7 to D-3. The dose will be 30 mg/m2/dose (adjusted for renal function). Melphalan: IV infusion over 30-60 minutes, depending on volume, on D-2. The dose will be 100mg/m2.Total body irradiation: 200 cGy AP/PA with 4MV or 6MV photons at 8 12 cGy/min at the point of prescription (average separation of measurements at mediastinum, abdomen, and hips) will be administered in a single fraction on day -1. Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Tacrolimus begins on Day 5, at least 24 hours after completion of posttransplantation Cy at 0.015mg/kg IBW/dose IV over 3 hours every 12 hours. Mycophenolic acid mofetil (MMF) F will be given at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).

Refractory and/or Relapsed Metastatic Solid Tumors

Cyclophosphamide

Fludarabine

low dose total body irradiation

Melphalan

Tacrolimus

Johns Hopkins All Children's Hospital

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Albert Einstein College of Medicine, Children's Hospital at Montefiore

New York Medical Center/ Maria Fareri Children's Hospital

Levine Cancer Institute/ Atrium Health

Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

A Phase II Trial of Reduced Intensity Conditioning and Partially HLA-mismatched (HLA-haploidentical) Related Donor Bone Marrow Transplantation for High-risk Solid Tumors

Safety of shortened duration immunosuppression assessed by the number of participants with non-relapse mortality (NRM) and grade III-IV acute graft versus host disease (Przepiorka criteria stages the degree of organ involvement in the skin, liver and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least sever and Stage 4+ being most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, liver 4+))

Overall survival in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Cumulative incidence by competing risks analysis of relapse in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Time from start of intervention to death without relapse in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Number of months from start of intervention until first adverse event as defined as relapse/disease progression or death by CTCAE v5.0 in participants receiving reduced intensity conditioning haploBMT

Number of months alive without progression in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Number of months alive without progression (as defined by RECIST, Any new lesion or increase of a measurable lesion by >25%; previous negative marrow positive for tumor. ** MIBG scan must be negative for patient to be classified as having a complete response. New site of disease documented by MIBG scan qualifies patient as having progressive disease.) in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

To determine the cumulative incidence by competing risks analysis of acute GVHD as defined by Przepiorka criteria stages the degree of organ involvement in the skin, liver and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least sever and Stage 4+ being most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, liver 4+)

To determine the cumulative incidence by competing risks analysis of chronic GVHD as defined by the NIH Consensus criteria

To document any unexpected toxicities after RIC haploidentical BMT.

To compare the tumor microenvironment, circulating tumor cells, and expression of MHC antigens as well as tumor specific antigens pre- and post BMT

To document the incidence of significant viral, bacterial and fungal infections as defined by the NCI's Common Terminology Criteria for Adverse Events (CTCAE) as well as the fungal criteria (proven and probable)

% of patients achieving donor bone marrow chimerism >/= 95% at Day 60

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Blood, throat swab, nasopharyngeal aspiration, and rectal swab will be obtained during acute illness and at convalescence (about 2 weeks after discharge). These specimens will be processed for viral isolation, bacterial culture and toxin detection, PCR, subtractive cloning, VIDISCA, gene chips, peptide library, cytokine/chemokine measurement, antibody detection for specific pathogens, etc. Questionnaire for contact history and clinical symptoms will be performed.

Kawasaki Disease

National Taiwan University Hospital

Etiology Study of Kawasaki Disease

Etiology Study of Kawasaki Disease--A Prospective Household and Case Control Study

The mean age of the 226 KD cases was 2.07 years, and the male to female ratio was 1.43 (133 boys to 93 girls). Their mean fever duration was 7.5 days with a mean peak temperature of 39.7°C. In addition to the typical symptoms of fever, neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation, these KD cases also exhibited cough (69%), rhinorrhea (58%), and diarrhea (45%). Cases of KD had a significantly higher positive rate of viral isolation in comparison with the control group (7.5% vs. 2.2%, p = 0.02). Compared with the control group, cases of KD were more likely to have overall positive rates of viral PCR (50.4% vs. 16.4%, p < 0.001) and for various viruses including enterovirus (16.8% vs. 4.4%, p < 0.001), adenovirus (8.0% vs. 1.8%, p = 0.007), human rhinovirus (26.5% vs. 9.7%, p < 0.001), and coronavirus (7.1% vs. 0.9%, p = 0.003).

Donors (n = 30) were matched first degree relatives who were eligible to donate peripheral blood stem cells.

Recipients (n=30) were enrolled to receive peripheral blood stem cells (PBSC) and receive either cyclosporine or tacrolimus and sirolimus for graft versus host disease (GVHD) prophylaxis.

Donors (n=30) were matched first degree relatives who were eligible to donate peripheral blood stem cells.

Arm 1-Sibling Donors

Arm 2-Recipients

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

(c) Up-front regimen included autologous stem cell transplantation.

Number of Prior Regimens of Participants that Received Stem Cell Transplant

Number of Prior Regimens of Participants that Did Not Receive Stem Cell Transplant

Participants who Received Stem Cell Transplant Disease Status at Enrollment

Participants who Did Not Receive Stem Cell Transplant Disease Status(Progressive Disease)/Enrollment

This list includes the disease status of participants who received stem cell transplant.

Disease Status at Hematopoietic Stem Cell Transplant

This list includes the disease status of participants who did not receive stem cell transplant.

Disease Status (Progressive Disease) at Hematopoietic Stem Cell Transplant

aRMS indicates alveolar rhabdomyosarcoma; ESRT, Ewings sarcoma; DSRCT, desmoplastic small round cell tumor.

Diagnosis (Participants that Received Stem Cell Transplant)

ESRT, Ewings sarcoma; DSRCT, desmoplastic small round cell tumor.

Diagnosis (Participants that Did Not Receive Stem Cell Transplant)

B/BM indicates bone or bone marrow metastases; ER, early recurrence; MR, multiply recurrent; PP, primary progressive disease.

High-Risk Features (Participants that Received Stem Cell Transplant)

High-Risk Features (Participants that Did Not Receive Stem Cell Transplant)

Engraftment is defined as rapid conversion to complete donor chimerism and is assessed by blood counts and chimerism, >95% donor engraftment at day 100 in >75% of patients.

Number of Participants With Engraftment

Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

Toxicity

Acute GVHD as by Modified Glucksberg Criteria occurring before day 100. Chronic GVHD as per Seattle criteria occurring after day 100.

Recipients -Cyclosporine GVHD Prophylaxis

Recipients -Tacrolimus/Sirolimus GVHD Prophylaxis

Number of Participants With Acute and Chronic GVHD

Days for participants to achieve a neutrophil count of 500/mm(3).

Median Time to Reach Absolute Neutrophil Count of 500/mm(3)

Days for participants to achieve a platelet count of 50,000/mm(3).

Median Time to Reach a Platelet Count of 50,000/mm(3)

Participants who experienced recurrence or progression of disease following transplant.

Early Post Transplantation Relapse

Progression free survival was based on the time from on-study date until progression or last follow-up.

Median Progression Free Survival

Participants who are alive at two years following Allo-Hematopoietic Stem Cell Transplant.

Two Year Survival Rate for Patients Undergoing Allo-Hematopoietic Stem Cell Transplant

Participants who tolerated the transplantation regimen and accepted >95% of the donors blood, marrow, and/or tissue.

Number of Participants to Complete Conversion to >95% Donor Chimerism

The median CD4 count with a range of 85-1565 (absolute count) was used to determine recovery and were considered recovered if in this range. The CD4 count was established by flow cytometry testing.

Cluster of Differentiation 4 (CD4) Reconstitution

Response is defined by the Response Evaluation Criteria in Solid Tumors (RECIST). RECIST criteria offer a simplified, conservative, extraction of imaging data for wide application in clinical trials. They presume that linear measures are an adequate substitute for 2-D (dimensional) methods and registers four response categories: Complete response (CR) is disappearance of all target lesions. Partial response (PR) is 30% increase in the sum of the longest diameter of target lesions. Progressive disease (PD) is 20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) is small changes that do not meet above criteria. For the purposes of this study very good partial response ((VGPR) is >75% reduction in disease) was also employed.

Best Response Post-Hematopoietic Stem Cell Transplant EOCH (Etoposide, Vincristine, Cyclophosphamide, and Doxorubicin)

Median survival from date of progression is based on the time from on-study date until progression or last follow-up.

Median Survival From Date of Progression

GVT is defined as tumor response after day 42 post-transplantation without cytotoxic therapy.

Number of Participants Who Experienced Graft Versus Tumor Effect (GVT)

Site of radiotherapy (high energy radiation) and/or toxicity experienced by the participants post HSCT radiotherapy. Grading was preformed using the Modified Glucksberg Criteria.

Post-Hematopoietic Stem Cell Transplant (HSCT) Radiotherapy

Donors (n = 30) were matched first degree relatives who were eligible to donate peripheral blood stem cells.In period 1 they donated cells.

Sibling Donors

In period 1 recipients received EPOCH-F/chemotherapy. In period 2 recipients received peripheral blood stem transplant.
Post transplant recipients received cyclosporine for GVHD prophylaxis.

Recipients Cyclosporine GVHD Prophylaxis

In period 1 recipients received EPOCH-F/chemotherapy. In period 2 recipients received peripheral blood stem transplant.
Post transplant recipients received tacrolimus & sirolimus for GVHD prophylaxis.

Recipients Tacrolimus /Sirolimus Prophylaxis

Period 1

Period 2

Dr. Terry Fry

Sarcoma

F-18 Fluorodeoxyglucose

Lymphocyte cells are collected from a healthy donor by apheresis and infused into the patient with a central venous catheter.

therapeutic allogeneic lymphocytes

Induction - 750 mg/m^2 intravenous (IV) infusion over 30 minutes x 1 dose. Day 5.
Transplant - 1200 mg/m^2 per day IV infusion over 2 hours daily for 4 days; days -6, -5, -4, -3.

cyclophosphamide

6 mg/kg per dose orally every other day (no day 9 dose).

cyclosporine

Induction - 10 mg/m^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days. Days 1, 2, 3, 4.

doxorubicin hydrochloride

50 mg/m^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days. Days 1, 2, 3, 4.

etoposide

Induction - 25 mg/m^2 per day intravenous (IV) infusion over 30 minutes daily for 3 days. Days 1, 2, 3.
Transplant - 30 mg/m^2 per day IV infusion over 30 minutes daily for 4 days; days -6, -5, -4, -3.

fludarabine phosphate

Transplant - 100 mg/m^2 per day intravenous (IV) infusion over 15 minutes for 1 day; day -2.

melphalan

Induction - 60 mg/m^2 per day in 2-4 divided doses by mouth daily for 5 days; days 1, 2, 3, 4, 5.

prednisone

Initiated on day +3. Patients >40kg, the initial dose will be 2 mg every 24 hours orally. Patients <40 kg, the initial dose will be 1 mg/m^2.

sirolimus

Day -1 at least 24 hours before the stem cell infusion at a dose of 0.03 mg/kg/day as a continuous infusion. Twelve hours later oral dose initiated at a dose of 0.1-0.15 mg/kg/day in two divided doses every 12 hours.

tacrolimus

Induction - 0.4 mg/m^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days; 1, 2, 3, 4.

vincristine sulfate

Stem cells from a healthy donor are collected and transplanted into the patient using a central venous catheter.

rhabdomyosarcoma/حمى

Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

Etiology Study of Kawasaki Disease

Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas

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